Mitochondrial fission

A process by which a mitochondrion divides into two or more smaller mitochondria

Mitochondrial fission

Mitochondria in HeLa cells visualized with GFP

Mitochondrial fission is a cellular process that involves the division of a mitochondrion into two or more smaller mitochondria. This process is crucial for maintaining the proper function and distribution of mitochondria within a cell. Mitochondrial fission is balanced by mitochondrial fusion, and together, these processes regulate the size, shape, and number of mitochondria, which are essential for cellular energy production and apoptosis.

Mechanism

Mitochondrial fission is mediated by a group of proteins that coordinate the constriction and division of the mitochondrial membrane. The key protein involved in this process is Dynamin-related protein 1 (Drp1), which is recruited to the outer mitochondrial membrane by receptor proteins such as Fission 1 (Fis1) and Mitochondrial fission factor (Mff). Once recruited, Drp1 forms a spiral around the mitochondrion, constricting it until the membrane divides.

Biological significance

Mitochondrial fission plays a critical role in several cellular processes:

• Cell division: During mitosis, mitochondria must be evenly distributed between daughter cells. Fission ensures that mitochondria are appropriately partitioned.
• Apoptosis: Mitochondrial fission is involved in the early stages of apoptosis, where it facilitates the release of cytochrome c and other pro-apoptotic factors.
• Response to stress: Cells undergoing stress may increase mitochondrial fission to remove damaged mitochondria through mitophagy, a selective form of autophagy.

Regulation

The balance between mitochondrial fission and fusion is tightly regulated by various signaling pathways. Post-translational modifications of Drp1, such as phosphorylation, ubiquitination, and SUMOylation, can modulate its activity and, consequently, the rate of fission. Cellular energy status, calcium levels, and reactive oxygen species (ROS) are also known to influence mitochondrial dynamics.

Pathological implications

Dysregulation of mitochondrial fission has been implicated in several diseases:

• Neurodegenerative diseases: Abnormal mitochondrial fission is associated with conditions such as Parkinson's disease and Alzheimer's disease, where it contributes to neuronal cell death.
• Cardiovascular diseases: Excessive mitochondrial fission can lead to cardiomyopathy and heart failure.
• Cancer: Altered mitochondrial dynamics are observed in cancer cells, where they may contribute to metabolic reprogramming and resistance to apoptosis.

Related pages

• Mitochondrial fusion
• Mitochondrial dynamics
• Mitophagy
• Dynamin-related protein 1