How Mitochondrial Dynamism Orchestrates Mitophagy

Orian S. Shirihai, Moshi Song, Gerald W. Dorn II

#explainpaper @explainpaper

Understanding the Significance of Mitochondrial Fission and Fusion

Mitochondrial dynamics refers to the movement of #mitochondria within a cell. This includes #fission, which is when mitochondria divide into two parts, #fusion, which is when two mitochondria join together, and #translocation, which is when mitochondria move from one part of the #cell to another.

This movement is important for maintaining the stability of the mitochondrial #DNA, which is the genetic material found in mitochondria, and for controlling the cell's #respiration. It can also be involved in programmed #CellDeath. In the #heart, mitochondrial dynamics #protein s, such as #mitofusin s, optic #atrophy, and dynamin-related protein, are highly expressed and play an important role in maintaining the quality of the #mitochondria.

Other roles for mitochondrial dynamics proteins in the #heart include helping to move #calcium into the mitochondria and regulating the structure of the mitochondria.

#Mitochondria are organelles in cells that are responsible for producing #energy. They can change their structure by breaking apart (#fission) and reforming (#fusion). This process is complicated and energy intensive, so it is important to understand why it is necessary.

One reason may be that when cells divide, the mitochondria need to be divided equally between the two daughter cells. This requires the #mitochondria to be broken apart and then reformed in each daughter #cell. This process of breaking apart and reforming is more efficient than growing and budding the mitochondria. To help explain this process, the authors use the analogy of an army.

Each soldier in the army is like a protein in the mitochondria, and the different units of the army are like the different parts of the #mitochondria. To increase the size of the army, units are added, rather than individual soldiers. This is similar to how mitochondria are modified, by adding or subtracting intact functional units, rather than individual #protein s.

Mitochondria are #organelle s in cells that can change their physical structure by undergoing fission.

Fission can be symmetrical, which is when mitochondria replicate and expand the number of #mitochondria in the #cell, or asymmetrical, which is when damaged components of the mitochondria are removed. The major #protein that helps with mitochondrial fission is called Drp1. It is mostly found in the #cytosol, but it needs to be recruited to the outer mitochondrial #membrane to help with fission.

Different factors can cause Drp1 to be recruited, such as phosphorylation by mitotic kinase cyclin B–cyclin-dependent-kinase (cdk) 1 complex during #cell division, or interacting with Bcl-2–associated protein x during #apoptosis. Inhibiting Drp1 can protect cells from some, but not all, forms of programmed cell death.

Mitochondria, which are organelles in cells, can be partitioned in #mitosis.

The most efficient way to do this is by dismantling and then reconstituting the cellular #mitochondria network through sequential #organelle fission, distribution, and refusion. To explain this concept, the text uses an analogy of how military units are constituted and managed within an army's hierarchical organization structure. In this analogy, each soldier represents an individual respiratory complex #protein, which are grouped together to form a squad (analogous to a respiratory complex).
Squads are arranged into platoons, and approximately 6 platoons comprise a functional unit, the company (like 1 complete respiratory chain). The text suggests that it would be easier to add prefabricated supercomplexes to preexisting ones, as by fusing mitochondrial cristae, rather than trying to make a larger or different shaped mitochondrion through the wholesale incorporation of individual proteins.

his is because making major structural modifications of respiratory supercomplexes on paracrystalline cristal membranes would first require destabilizing the #membrane, then incorporating additional individual #protein components, and finally reconstructing the original highly organized structure, which is complicated and potentially disruptive.

#Mitochondria are small organelles in cells that can change their physical structure by undergoing fission.

Fission can be symmetrical, which means the #mitochondria are split into two equal parts, or asymmetrical, which means the mitochondria are split into two unequal parts. Symmetrical fission is used to replicate and expand the number of mitochondria in the #cell, while asymmetrical fission is used to remove damaged mitochondria from the cell. The major #protein responsible for mitochondrial fission is called Drp1.
Drp1 is mostly found in the cytosol, but it needs to be recruited to the outer mitochondrial #membrane to promote fission. Different factors can stimulate Drp1 to move to the outer mitochondrial #membrane, such as phosphorylation by mitotic kinase cyclin B–cyclin-dependent-kinase (cdk) 1 complex. In addition, the endoplasmic reticulum (ER) is often found at the sites of mitochondrial fission.
The text is talking about the process of mitochondrial fission, which is a process that involves connecting and separating parts of a #mitochondria. The author uses the metaphor of making sausage links to explain the process, but then goes on to explain that mitochondria are actually more like a turducken, which is a dish made of a chicken stuffed inside a duck stuffed inside a turkey.
This creates layers of poultry, which is similar to the double #membrane /double space structure of #mitochondria. The author then explains that the process of mitochondrial fusion involves connecting the two mitochondria layer by layer, using proteins called mitofusins. Mitofusins have a #GTPase domain, two hydrophobic heptad repeat coiled-coil domains, and a small hydrophobic transmembrane domain.

These proteins insert into the outer #membrane of the #mitochondria, and can interact with other proteins in the cytosol. The process of mitochondrial fusion is GTP-independent and reversible, but #GTP #hydrolysis is essential for irreversible outer membrane fusion.

#Mitofusins are proteins that are essential for the first two stages of mitochondrial fusion, which is the process of two mitochondria joining together.

This process is important for the exchange of information between the #mitochondria and the #cell. If the mitofusins are deleted or suppressed, the mitochondria become abnormally small and are unable to undergo normal fusion. This can have serious implications for the health of the #cell.

Membrane-by-membrane mitochondrial fusion is a process that helps to keep the structure of the inner and outer membranes of #mitochondria intact.

This helps to preserve the process of oxidative phosphorylation, which is important for providing energy to cells. Without this process, molecules that can be toxic to cells can form and interrupt the electron transport chain. This process is also important for maintaining the normal shape of the crista, which is necessary for the proper assembly and functioning of electron transport chain supercomplexes.

In addition, it has been shown that interrupting Mfn-mediated OMM fusion can cause a #cardiomyocyte ER stress response, while interrupting Opa1-mediated IMM fusion can compromise mitochondrial function.

Mitochondrial fission and fusion are important processes in #biology, as evidenced by the fact that mutations in genes related to these processes can cause serious diseases in humans.

Altering the balance between fission and fusion can have an effect on the shape of #mitochondria, with more fusion leading to longer, more interconnected mitochondria, and more fission leading to shorter, less interconnected mitochondria. It is generally thought that more interconnected #mitochondria are healthier, but this is not always the case.

In some cases, mitochondrial #fragmentation can be beneficial, and it is important to understand the interplay between mitochondrial fragmentation and other processes, such as #mitophagy, in order to understand the effects of mitochondrial fission and fusion.

Mitophagy is a process by which cells eat their own #mitochondria. Mitochondria are organelles that produce energy in the form of #ATP, which is used to power most biological processes.

Over time, mitochondria can become damaged and produce toxic levels of reactive oxygen species ( #ROS ). To protect the #cell from this damage, it has developed a sophisticated system to identify and remove these dysfunctional #mitochondria. This process is called mitophagy. #Mitophagy is a combination of the words mitochondria and #autophagy, which means "self-eating". It is a way for cells to selectively target and remove damaged mitochondria, while still keeping healthy ones.