Posted on May 15, 2019 at 4:00 PM
Mitochondria are highly versatile and are able to change their shape through processes called fission and fusion. Fission is defined as the breaking apart of a single entity, whereas fusion is defined as the joining of two or more entities to form a whole. The processes of fission and fusion oppose each other and allow the mitochondrial network to constantly remodel itself. If a stimulus alters the balance of fission and fusion in a cell, it could significantly alter the mitochondrial network. For example, an increase in mitochondrial fission would result in the creation of many fragmented mitochondria. This is useful for eliminating damaged mitochondria and for creating smaller mitochondria for efficient transport to energy-demanding areas of the body. Therefore, achieving a balance between these mechanisms allows a cell to have a properly organized mitochondrial network during biogenesis and may have an important role in the adaptation of muscles to physiological stress (for example, during exercise).
For the Scientist: Fusion allows mitochondria to compensate for one another’s defects by sharing components and thereby helps maintain energy output in the face of stress. However, when a certain threshold of damage is reached, mitochondria are eliminated by autophagy. Fission segregates the most seriously damaged mitochondria to preserve the health of the mitochondrial network, in addition to regulating morphology and facilitating mitochondrial trafficking. The highly dynamic mitochondrial fusion and fission cycle is proposed to balance two competing processes: compensation of damage by fusion and elimination of damage by fission. Failure of these stress responses may lead to neuron death and neurodegenerative disorders.
In humans, mitochondrial fusion and fission are both controlled by GTPases of the dynamin family. The process of mitochondrial fission is directed by dynamin-related protein 1 (Drp1), a member of the cytosolic dynamin family. This protein forms a spiral around mitochondria and constricts to break apart both the outer and inner membranes of the organelle. In contrast, the process of fusion is directed by different membrane-anchored dynamin proteins at different levels of the mitochondria. Fusion at the level of the outer mitochondrial membrane is mediated by Mfn1 and Mfn2 (Mitofusins 1 and 2), and fusion at the level of the inner mitochondrial membrane is mediated by Opa1. Several studies have demonstrated a correlation of increased mitochondrial respiratory capacity with Mfn1, Mnf2, and Drp1 gene expression after endurance exercise. This evidence indicates that reorganization of the mitochondrial network in muscle cells plays an important role in the response to exercise.