mitochondrial fragmentation involved in apoptotic process

Definition

Target type: biologicalprocess

The change in the morphology of the mitochondria in an apoptotic cell from a highly branched network to a fragmented vesicular form. [GOC:mtg_apoptosis, GOC:rk, PMID:12867994]

Mitochondrial fragmentation, a critical step in apoptosis, is a tightly regulated process orchestrated by a complex interplay of proteins and signaling pathways. It begins with the activation of caspases, a family of cysteine proteases, triggered by apoptotic stimuli. Activated caspases cleave and activate pro-apoptotic members of the Bcl-2 family, such as Bax and Bak, leading to their translocation to the mitochondrial outer membrane. Once at the membrane, Bax and Bak oligomerize, forming pores that disrupt the integrity of the outer membrane. This permeabilization releases cytochrome c and other apoptogenic factors from the intermembrane space into the cytosol. Cytochrome c, in the cytosol, binds to the adaptor protein Apaf-1, activating caspase-9, which then activates the executioner caspases, caspase-3, -6, and -7. These caspases initiate a cascade of proteolytic events that dismantle the cell, leading to its demise.

The process of mitochondrial fragmentation itself involves the severing of the mitochondrial network, a dynamic interconnected structure, into smaller, isolated fragments. This fragmentation is mediated by the dynamin-related protein 1 (Drp1), a GTPase that assembles into ring-like structures around the mitochondrial fission sites. Drp1 recruitment to the mitochondria is regulated by various factors, including phosphorylation by kinases like cyclin-dependent kinase 1 (CDK1) and protein kinase A (PKA), as well as interactions with adapter proteins like Fis1 and Mff. Once recruited, Drp1 constricts the mitochondrial membrane, ultimately leading to its fission.

Mitochondrial fragmentation during apoptosis serves several key functions. Firstly, it increases the surface area of the mitochondrial outer membrane, facilitating the release of apoptogenic factors like cytochrome c. Secondly, it isolates damaged or dysfunctional mitochondria, preventing the spread of reactive oxygen species (ROS) and other harmful molecules to the rest of the cell. Thirdly, it physically separates the mitochondrial network, potentially preventing the activation of survival pathways that could counteract apoptosis.

Overall, mitochondrial fragmentation is a highly regulated and essential step in the apoptotic process. It is a tightly controlled event, involving the coordinated action of multiple proteins and signaling pathways, ensuring the efficient and timely elimination of cells that are no longer required or have become damaged.'
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Proteins (2)

Compounds (95)