#mitochondrial dynamics

Mitochondria, the energy-producing organelles of eukaryotic cells, are involved in a myriad of cellular functions beyond ATP production, including calcium homeostasis, reactive oxygen species (ROS) generation, apoptosis regulation, and the modulation of immune responses. In autoimmune diseases, mitochondrial dysfunction is increasingly recognized as a key factor in disease pathogenesis. These disorders, characterized by the immune system's aberrant recognition and attack on self-antigens, often manifest in conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). This article delves into the mechanisms linking mitochondrial dysfunction to autoimmune disorders, highlighting cellular changes, signaling pathways, and potential therapeutic approaches.

Mitochondrial Function in Immune Cells

Mitochondria are critical for cellular energy metabolism, primarily through oxidative phosphorylation, which occurs in the inner mitochondrial membrane and generates ATP. However, their roles extend far beyond energy production. Mitochondria are involved in immune cell activation, differentiation, and the regulation of apoptosis. Immune cells, including T lymphocytes, B lymphocytes, dendritic cells, and macrophages, rely on mitochondrial function for their metabolic demands during immune responses. These cells undergo rapid changes in mitochondrial dynamics and energy production during immune activation.

Mitochondria also produce ROS as byproducts of oxidative phosphorylation, and these ROS, under normal conditions, function as signaling molecules that regulate immune responses. However, excessive ROS generation, stemming from mitochondrial dysfunction, can lead to oxidative stress, damage to cellular components, and dysregulated immune responses that are characteristic of autoimmune diseases.

Mitochondrial Dysfunction and Autoimmune Pathogenesis

In autoimmune diseases, mitochondrial dysfunction contributes to disease progression through multiple interconnected mechanisms, including dysregulated immune responses, enhanced oxidative stress, impaired mitochondrial dynamics, and defective apoptosis. The following section outlines key mechanisms linking mitochondrial dysfunction to autoimmune pathogenesis.

1. Oxidative Stress and Immune Dysregulation

Mitochondria are a major source of ROS, which are produced as intermediates during oxidative phosphorylation in the electron transport chain (ETC). Under normal conditions, ROS are tightly regulated by antioxidant systems, including superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, in autoimmune diseases, mitochondrial dysfunction often results in increased ROS production, overwhelming the antioxidant capacity of the cell and resulting in oxidative stress.

Oxidative stress can damage cellular macromolecules such as lipids, proteins, and nucleic acids. In immune cells, excessive ROS lead to the activation of several signaling pathways, including the nuclear factor-kappa B (NF-κB) pathway, which promotes the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. In systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), ROS-induced activation of these inflammatory pathways amplifies the autoimmune response, driving tissue damage and inflammation.

Moreover, oxidative stress exacerbates the production of autoantibodies, particularly in diseases like SLE, where ROS contribute to the formation of immune complexes that target self-antigens, including nuclear components like double-stranded DNA (dsDNA) and mitochondrial antigens.

2. Mitochondrial Dynamics in Autoimmune Diseases

Mitochondrial dynamics, encompassing processes such as mitochondrial fission, fusion, and mitophagy, are critical for maintaining mitochondrial function and cellular homeostasis. Mitochondrial fission, mediated by proteins such as dynamin-related protein 1 (Drp1), leads to the division of mitochondria, while fusion, regulated by mitofusins (Mfn1/2) and optic atrophy 1 (OPA1), facilitates the merging of mitochondria to restore mitochondrial function and DNA integrity. Mitochondrial fusion is crucial for maintaining the respiratory capacity and metabolic flexibility of immune cells.

In autoimmune disorders, an imbalance in mitochondrial dynamics is often observed. For example, in rheumatoid arthritis (RA), T cells exhibit excessive mitochondrial fission and impaired fusion, leading to mitochondrial fragmentation, reduced mitochondrial membrane potential, and diminished oxidative phosphorylation capacity. This dysfunction contributes to the failure of immune cells to produce sufficient ATP during activation, resulting in altered cytokine production and a hyperactive immune response.

Similarly, in multiple sclerosis (MS), aberrant mitochondrial dynamics in oligodendrocytes and T cells contribute to neuroinflammation and demyelination. The dysregulated fission and fusion processes impair mitochondrial function, leading to increased oxidative stress, mitochondrial damage, and exacerbation of inflammatory cascades that damage myelin.

3. Mitochondrial-Derived Damage-Associated Molecular Patterns (DAMPs)

Mitochondria are also sources of damage-associated molecular patterns (DAMPs), which are intracellular molecules released upon cellular injury or stress. DAMPs, such as mitochondrial DNA (mtDNA), cardiolipin, and mitochondrial N-formyl peptides, serve as danger signals recognized by pattern recognition receptors (PRRs) on immune cells. These include toll-like receptors (TLRs), particularly TLR9, which recognizes mtDNA, and TLR2/4, which are involved in the recognition of mitochondrial lipids.

In autoimmune diseases, mitochondrial dysfunction leads to the release of mtDNA and other mitochondrial components into the extracellular space, where they act as endogenous ligands for PRRs. The activation of these receptors triggers inflammatory responses, including the activation of NF-κB, interferon pathways, and the inflammasome, all of which amplify immune responses and contribute to chronic inflammation and tissue damage.

In SLE, circulating mtDNA fragments have been detected in the serum, correlating with disease activity. The presence of mtDNA in the bloodstream is thought to exacerbate the activation of autoreactive immune cells and the production of autoantibodies, particularly those targeting nuclear antigens.

4. Impaired Apoptosis and Autoimmunity

Mitochondria are key regulators of apoptosis, particularly the intrinsic or mitochondrial pathway of cell death. The mitochondrial pathway is initiated by the release of pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF) from the mitochondrial intermembrane space into the cytosol. This release activates caspases, leading to cell death. In autoimmune diseases, mitochondrial dysfunction often leads to defective apoptosis, which prevents the elimination of autoreactive immune cells.

In diseases like systemic lupus erythematosus (SLE), defective apoptosis of T cells and B cells contributes to the survival of autoreactive lymphocytes that would normally be eliminated through programmed cell death. The persistence of these cells results in the production of autoantibodies, including anti-dsDNA and anti-mitochondrial antibodies, which target self-tissues and exacerbate inflammation.

Moreover, impaired mitophagy, the process by which damaged mitochondria are selectively degraded by autophagy, further contributes to the accumulation of dysfunctional mitochondria, promoting sustained oxidative stress and inflammation.

Mitochondrial Dysfunction in Specific Autoimmune Disorders

1. Systemic Lupus Erythematosus (SLE)

In SLE, mitochondrial dysfunction plays a pivotal role in disease pathogenesis. Increased ROS production, defective mitophagy, and impaired apoptosis contribute to the activation of autoreactive T cells and B cells, leading to the production of autoantibodies. The release of mitochondrial DAMPs, such as mtDNA, amplifies the inflammatory response, and mitochondrial damage is directly linked to the severity of disease activity in SLE.

2. Rheumatoid Arthritis (RA)

In RA, mitochondrial dysfunction in immune cells, particularly in synovial T cells and macrophages, is associated with increased mitochondrial fragmentation, oxidative stress, and dysregulated immune activation. ROS and mitochondrial-derived DAMPs contribute to the chronic inflammatory environment in the synovium, driving the production of pro-inflammatory cytokines and promoting joint destruction.

3. Multiple Sclerosis (MS)

Mitochondrial dysfunction in MS primarily affects oligodendrocytes, the myelinating cells in the central nervous system. Impaired mitochondrial function in these cells contributes to neuroinflammation and demyelination. Additionally, T cells with dysfunctional mitochondria play a role in the perpetuation of inflammation, leading to the destruction of myelin and axonal injury in the CNS.

Therapeutic Implications

Targeting mitochondrial dysfunction presents a promising therapeutic strategy for autoimmune diseases. Potential approaches include:

Mitochondrial Antioxidants: Compounds like MitoQ, MitoTEMPO, and other mitochondrial-targeted antioxidants can help reduce oxidative stress, protect mitochondrial function, and alleviate inflammation.

Modulating Mitochondrial Dynamics: Agents that promote mitochondrial fusion or inhibit excessive fission, such as Mfn2 activators, could restore mitochondrial integrity in immune cells, reducing inflammation and improving immune regulation.

Enhancing Mitophagy: Stimulating mitophagy through compounds such as spermidine or activation of the PINK1/PARK2 pathway may help remove damaged mitochondria and reduce the accumulation of mitochondrial DAMPs.

Targeting Mitochondrial DAMPs: Inhibiting the release of mtDNA and other mitochondrial DAMPs using TLR inhibitors or blocking downstream signaling pathways may reduce the inflammatory response in autoimmune diseases.

Conclusion

Mitochondria are integral organelles responsible for various critical cellular functions, primarily energy production through oxidative phosphorylation. They are involved in maintaining cellular homeostasis, regulating metabolism, modulating calcium levels, and controlling apoptosis. Emerging evidence has highlighted mitochondrial dysfunction as a key contributor to a variety of diseases, including arthritis. This formal overview aims to explore the complex relationship between damaged mitochondria and arthritis, focusing on the molecular mechanisms that link mitochondrial dysfunction to the pathogenesis of inflammatory joint diseases, particularly rheumatoid arthritis (RA) and osteoarthritis (OA).

Mitochondrial Structure and Function

Mitochondria are double-membraned organelles found in eukaryotic cells, and they are crucial for cellular energy metabolism. Their primary role is the production of adenosine triphosphate (ATP) via oxidative phosphorylation, a process that takes place in the inner mitochondrial membrane. During this process, the electron transport chain (ETC) generates a proton gradient across the inner membrane, which drives ATP synthesis through ATP synthase. However, this process also generates reactive oxygen species (ROS) as byproducts, primarily from complexes I and III of the ETC. Under normal physiological conditions, ROS are neutralized by antioxidants, including superoxide dismutase (SOD), catalase, and glutathione. However, under pathological conditions, excessive ROS production can lead to oxidative stress, contributing to cellular damage and dysfunction.

In addition to ATP production, mitochondria have essential roles in calcium buffering, apoptosis regulation, and the maintenance of cellular integrity. Damage to these organelles disrupts these functions, contributing to various diseases, including arthritis.

Mitochondrial Dysfunction in Arthritis

Arthritis is a group of diseases characterized by inflammation and degeneration of the joints. It includes conditions like rheumatoid arthritis (RA), an autoimmune disease, and osteoarthritis (OA), a degenerative disease. In both types of arthritis, mitochondrial dysfunction has been identified as a critical factor that exacerbates disease progression through several mechanisms, including increased oxidative stress, immune activation, and tissue damage.

1. Oxidative Stress and Mitochondrial Damage

Oxidative stress is a hallmark of both RA and OA, and mitochondria are central to its production. In these conditions, mitochondrial dysfunction results in an increase in ROS production, overwhelming the cell’s antioxidant defenses. This oxidative stress leads to the modification of cellular structures, including proteins, lipids, and DNA, causing further mitochondrial damage. In RA, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) stimulate immune cells like macrophages and neutrophils to release large amounts of ROS. These ROS contribute to the local inflammatory environment and accelerate joint destruction by damaging mitochondria and amplifying oxidative stress.

Mitochondrial damage results in a feedback loop where impaired mitochondrial function generates more ROS, further promoting inflammation. For instance, in RA, markers of oxidative damage such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) have been found to correlate with disease activity, suggesting a direct relationship between mitochondrial dysfunction and disease severity.

2. Mitochondrial DNA Damage and Inflammatory Signaling

Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative damage due to its proximity to the ETC, where ROS are produced during ATP synthesis. Unlike nuclear DNA, mtDNA is not protected by histones and has limited repair mechanisms, making it prone to mutations. Damage to mtDNA impairs mitochondrial function and can lead to the release of mtDNA fragments into the cytoplasm or extracellular space.

In the context of arthritis, mtDNA damage has been implicated in immune activation. When damaged mtDNA is released into the cytoplasm, it is recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), on immune cells. TLRs, particularly TLR9, activate downstream inflammatory signaling pathways that lead to the production of pro-inflammatory cytokines such as TNF-α and IL-6. This further exacerbates the inflammatory response in joints and contributes to the progression of arthritis. Studies have shown that the presence of mtDNA fragments in the serum of RA patients correlates with disease activity, indicating the role of mtDNA in driving inflammation.

3. Mitochondrial Dynamics and Arthritis Pathogenesis

Mitochondrial dynamics refer to the continuous processes of mitochondrial fission (division) and fusion (joining), which maintain mitochondrial function and integrity. Fission allows for the removal of damaged mitochondria, while fusion helps to integrate mitochondrial contents and maintain a healthy mitochondrial pool. Imbalance between fission and fusion is associated with several diseases, including arthritis.

In the case of RA, excessive mitochondrial fission and reduced fusion have been observed. This imbalance results in mitochondrial fragmentation, which impairs mitochondrial function, increases ROS production, and contributes to cellular stress. Fission is regulated by proteins such as dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1), while fusion is controlled by mitofusins (Mfn1 and Mfn2) and optic atrophy 1 (OPA1). Dysregulation of these proteins in RA leads to a fragmented mitochondrial network, which exacerbates oxidative stress and inflammation in synovial tissues.

4. Mitochondrial-Dependent Cell Death

Mitochondria are also central regulators of programmed cell death, particularly apoptosis. In the pathogenesis of arthritis, excessive or dysregulated apoptosis contributes to joint destruction. Mitochondrial dysfunction plays a critical role in the intrinsic apoptotic pathway by releasing pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF). These factors activate caspase-dependent and caspase-independent pathways, leading to the death of synovial cells and cartilage cells, which contributes to the progressive tissue damage observed in both RA and OA.

Furthermore, mitochondrial permeability transition pore (mPTP) opening, which is induced by oxidative stress, can lead to necrosis, a form of uncontrolled cell death. Necrotic cell death in the joints increases inflammation and tissue degradation, particularly in OA, where cartilage breakdown is a hallmark feature.

Therapeutic Approaches Targeting Mitochondrial Dysfunction in Arthritis

Given the significant role of mitochondrial dysfunction in the pathogenesis of arthritis, various therapeutic strategies aimed at improving mitochondrial function are under investigation.

1. Mitochondrial Antioxidants

Mitochondrial-targeted antioxidants, such as MitoQ and MitoTEMPO, have been developed to selectively accumulate in mitochondria, where they can neutralize ROS and reduce oxidative stress. These compounds have shown promise in preclinical models of arthritis, where they help to reduce inflammation, protect mitochondrial function, and limit joint damage. The use of mitochondrial antioxidants could be an effective strategy to mitigate oxidative stress in arthritic conditions.

2. Mitochondrial Biogenesis Enhancement

Another potential therapeutic approach is the activation of mitochondrial biogenesis, the process by which new mitochondria are formed to compensate for damaged mitochondria. Agents that activate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of mitochondrial biogenesis, could help restore mitochondrial function in arthritic tissues. Compounds such as resveratrol and NAD+ precursors are under investigation for their ability to promote mitochondrial biogenesis and improve cellular metabolism in arthritis.

3. Mitochondrial Dynamics Modulation

Restoring the balance between mitochondrial fission and fusion is another therapeutic strategy. Inhibiting excessive mitochondrial fission or promoting mitochondrial fusion may help maintain mitochondrial integrity and reduce inflammation in arthritis. Drugs targeting Drp1 or enhancing Mfn1/Mfn2 activity are potential candidates for modulating mitochondrial dynamics in arthritic diseases.

4. Mitophagy Enhancement

Mitophagy, the selective autophagic degradation of damaged mitochondria, is essential for maintaining mitochondrial quality. Enhancing mitophagy through the use of compounds like spermidine or activators of the PINK1/PARK2 pathway could help eliminate dysfunctional mitochondria and reduce inflammation, making it a promising therapeutic approach in arthritis.

Conclusion

Biology Concepts – mitochondrial dynamics

Stars are the largest fusion reactors around, and organisms do use 

some of the energy our Sun produces by joining two hydrogen atoms

into a helium atom - remember photosynthesis? Fission reactors are 

closer to home, but are much less efficient -- and can melt down

and kill us all.  Cellular fission and fusion are about joining and 

splitting things as well, just without the release of energy.

In the typical picture of a working cell, you would see millions of vacuoles traveling around, joining together and splitting off from organelles. The general proposition is that a bag of stuff fuses(joins) or fissions (separates) from another bag of stuff. In physics, fission and fusion can be sources of great energy, but in cells they usually require an input of energy. If the processes were the same, we could run the world’s electronics on biology power – a true cell phone!

Fusing and fissioning are easy for vacuoles, they have one membrane. But the mitochondria and chloroplasts we have been looking at for the past few posts have very specific, double membrane structures. The outer membrane and inner membranes form a intermembrane space that is crucial for their function, and the inner membranes have specific forms and structures that are necessary to make carbohydrate or ATP.

Wouldn’t fusing or splitting these organelles destroy the membrane structures needed to maintain their functions? Indeed, the typical cartoon of the cell shows individual mitochondria or chloroplasts floating around in the cell, doing their jobs, but not interacting with the other organelles or with each other.

The structure pictured in green is, believe, it or not, the

mitochondrion of a fibroblast (fibro = fiber and blast =

sprout) cell, one that makes connective tissue. This doesn’t

look much like the mitochondrion in the biology books,

does it? The different strands join together and separate

constantly.

For mitochondria at least, this picture is misleading. In many cells, the mitochondria do not look like independent structures floating within the cell. They look more like strands of spaghetti on your plate. Mitochondria can also move around, they fuse together and break apart, they are recruited to different subcellular areas based on energy need, and they can exchange organellar content.

All these features (shape, communication, movement, fusion, fission, and exchange) are dynamic, meaning that they change with time and are regulated. First recognized as a regulated process about 10 years ago, this has spawned a new line of research called mitochondrial dynamics.

Changes in morphology are also involved in progression through the cell cycle. A 2009 study showed that in cultured cells, the mitochondria must fuse together into branched networks in order for the cell to enter the phase when it replicates its DNA. Now it appears that this changing mitochondrial morphology is important for other shifts in cell fate. The same group that conducted the 2009 study above showed in May 2012 that mitochondrial fusion and fission are important for oogenesis differentiation (the changes an egg goes through to become different types of cells) in fruit fly egg chambers, implying their importance in differentiation of other cells too.

It appears that fusion and fission help to maintain the correct number of mitochondria, but also work in the preservation of mitochondrial function. Defective proteins can be kicked out if there are normal proteins to replace them. Fusion of mitochondria can provide these normal proteins. In other instances, low oxygen or low carbohydrate concentrations can bring fission and fusion so that the mitochondria can share nutrients and prevent their own degradation.

Most importantly, defective mitochondrial DNA (mtDNA) can be minimized by combining or being replaced it with normal DNA from functioning mitochondria. In most cases, recombination of DNA serves to increase genetic diversity, but with mtDNA it seems the opposite effect is desired. Recombining and exchanging DNA serves to maintain a single uniform genome for all the mitochondria; fusion can preserve the integrity of the mitochondrial genome. Mutations or defects in either exchange, fission, or fusion systems result in poor mitochondrial function and identifiable diseases.

People with Charcot-Marie Tooth have very high

arches, and are most often double jointed. Would

you enjoy having your knees bend the other

direction? I can tell you from personal experience,

that double jointed people are very hard to wrestle

against. They can slip out of whatever hold you try

on them.

If the fusion of mitochondria is defective, a disease called Charcot-Marie-Tooth type 2a may result.  This is a neuronal degenerative disease that usually affects the lower extremities more than the arms. Most cases are caused by defects in the cells that surround the neural axon (the long projection between the cell body and the connection point to other neurons), but in type 2a, the defect is in the axon, specifically the inability of mitochondria to fuse. Therefore, fusion must be important.

In Huntington’s disease, there is too much mitochondrial fission. Huntington’s chorea (chorea = dance, patients with this disease develop large uncontrollable movements that make it look like they are dancing). The cause is an expansion in the huntingtin gene (yes, I spelled it right); a three DNA base repeat (CAG) is mutated and becomes repeated too many times. This affects the function of the huntingtin protein. The age of onset and speed of progression are related to how expanded the triplet repeat is. As of today, this autosomal dominant genetic disease (only need to inherit one mutant gene for it to occur) is untreatable and fatal.

However, the mechanism by which this mutation causes neuron degeneration is just becoming clear.  A 2010 study indicated that the mutant huntingtin protein interacts with the proteins that control mitochondrial fission and makes them overactive. Too much fission disrupts mitochondrial functions and the neurons become defective and then die.

Even more important, in terms of numbers of people affected, is the link between reduced mitochondrial fission and Alzheimer’s disease. Scientists know that it was the build up of amyloid protein that promotes neuron degeneration, but until recently, they didn’t know how it was occurring. It turns out that the plaque proteins can stimulate nitric oxide production, which then damages the fission proteins of the mitochondria.

DRP1 proteins are important for the fission of a

mitochondrion into two mitochondria. They oligomerize

(join together in groups) and pinch the mitochondria

apart. Nitric oxide can damage the DRP1 proteins – so

no mitochondrial fission.

This is huge news because preventing this nitric oxide damage might be a way to slow or stop Alzheimer’s progression. This is a difficult area of research, since nitric oxide is important in many biochemical pathways; just shutting down nitric oxide production everywhere in the body would lead to defective hair growth, blood vessel pressure control, abnormal blood clotting and atherosclerosis, ……oh, and Viagra wouldn’t work either.

The movement of mitochondria within cells is also crucial for their function. The longest cells in your body are your motor neurons. A single cell can be several feet long. Your mitochondria must get to where they are needed along the axon of the neuron, and this requires regulated transport and communication.

Defective transport is one outcome during Charcot-Marie-Tooth type 2a defective mitochondrial fusion and in overstimulation of mitochondrial fission in Huntington’s disease. In addition, defective axonal transport of mitochondria may turn out to be an important early defect in Alzheimer’s disease. In fact, defective transport of mitochondria may play a role in Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other neurodegenerative diseases that involve defective mitochondrial fusion and fission.

Why might this be….. I’m not sure, but here is a guess. Defective fusion or fission leads to defective function – defective function leads to reduced ATP formation – reduced ATP results in defective energy-requiring functions of the cell, like transport of mitochondria from one place to another. I have no evidence for this, but it is a logical, testable hypothesis. It could be that defective transport is an effect, not a cause, of these diseases -at least in part.

Two of our more famous Parkinson’s patients;

Muhammed Ali and Michael J. Fox. Float like Marty McFly and sting like a bee?

For Parkinson’s disease, a 2009 study showed that defective mitochondrial transport occurred due to dysfunction in the fusion/fission system, independent of changes in the ATP level. However, ATP production is not the only function of mitochondria. They also work in regulating the amount of calcium in the cell, and altered calcium levels can lead to disruption of the cytoskeletal transport mechanisms. Maybe I need to tweek my hypothesis; it is fusion/fission-mediated defects in several mitochondrial functions that then cause axonal transport changes that are noted in many neurodegenerative disorders. Now design an experiment to test it - this is how scientists go about their work.

So we see that the mitochondria are not static, they are changing all the time and that these changes are crucial for their function and integrity. Here is our exception in the similarities of chloroplasts and mitochondria. It would seem, at least based on current evidence, chloroplasts are relative loners.

This is not to say that can’t be dynamic. We have seen that chloroplasts have a definitive inheritance pattern, either maternal or paternal, and they will fight to maintain this pattern. Chloroplast fusion has been most often described in the zygote(initial cell formed by fusion of the gametes during fertilization, from Greek zygota = joined or yoked together) of algae. In these cases, which are still rare, the chloroplast genome of one of the two fused organelles will be degraded. Fusion of other chloroplasts, as in mature plant cells, either does not occur or has not been studied, because I can’t find any publications describing it.

These are examples of the dynamic activities of chloroplasts.

Stromuleconnections can be formed between chloroplasts for

the passage of organelle contents. They are usually 0.5 microns

in diameter (1/500,000 of a meter) and can be found in all types

of plastids. Their function – not completely known yet.

On theother hand, chloroplasts aren’t complete loners either. As far back as the 1960’s there were reports saying that chloroplasts might have certain connections at certain times. More recent studies indicate that small connections can be formed between chloroplasts, often called tubular connections or stromules. It is interesting that stromules can be formed between chloroplasts and mitochondria. It is believed that this is one way the plant cell keeps these two organelles close to one another, since their functions, products, and by-products are so interrelated.

You might ask why the mitochondria and chloroplasts that have so much in common differ in their relative dynamic properties. They were both once free organisms that had to have lots of interactions with other members of their species, but only the mitochondria seemed to have preserved it.  Next week, we will look into how this mitochondrial dynamism is even more crucial organism survival – by regulating cell death. Believe it or not, cells have to know how to die well.

Kasturi Mitra, Richa Rikhy, Mary Lilly, and Jennifer Lippincott-Schwartz (2012). DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis J Cell Biol DOI: 10.1083/jcb.201110058

For more information or classroom activities on mitochondrial dynamics or cellular differentiation, see:

Mitochondrial dynamics –

http://mitodyn2011.azuleon.org/

http://www.its.caltech.edu/~chanlab/main%20pages/research.html

http://www.youtube.com/watch?v=0NmBaw3grr4

http://www.plantmitochondria.net/Plant_Mitochondria/Movies.html

http://www.nature.com/scitable/topicpage/mitochondrial-fusion-and-division-14264007

http://biology.about.com/b/2010/04/23/mitochondrial-fusion.htm

http://www.sciencedaily.com/releases/2010/04/100415125942.htm

http://www.sciencedaily.com/releases/2011/01/110124162712.htm

http://www.ellisonfoundation.org/content/does-mitochondrial-fusion-protect-against-mitochondrial-dna-mutations-during-aging

www.its.caltech.edu/~chanlab/PDFs/Griffin_et_al_BBA_2006.pdf