Mitochondrial fragmentation (MF)

Mitochondrial fragmentation is a biological process characterized by the division of a single mitochondrion into two or more smaller, often spherical daughter mitochondria. While fission is a normal physiological component of mitochondrial dynamics necessary for organelle inheritance and quality control, excessive fragmentation is a hallmark of cellular stress and pathological states. This process is primarily mediated by the recruitment of Dynamin-1-like protein (DRP1) from the cytosol to the mitochondrial outer membrane, where it forms a ring-like structure that constricts and severs the organelle in a GTP-dependent manner (PMID: 28441113, PMID: 31217514). Pathological mitochondrial fragmentation is strongly associated with the initiation of apoptosis and the progression of various chronic conditions, including neurodegenerative diseases like Parkinson's and Alzheimer's, as well as acute events like cardiac ischemia-reperfusion injury (PMID: 21760631). Pharmacological strategies often focus on inhibiting the mediators of fission, such as DRP1 or its membrane adaptors (Fis1, MFF, MiD49/51), to preserve mitochondrial network integrity and cell viability. Although 'Mitochondrial fragmentation' is a description of a cellular phenotype rather than a single molecular target, it serves as a critical focal point for drug development aimed at restoring mitochondrial health (PMID: 29202511).

Other names

Mitochondrial fissionMitochondrial scissionMitochondrial decayExcessive mitochondrial fission

Inhibition of Dynamin-1-like protein (DRP1) recruitment to the mitochondrial outer membrane or inhibition of DRP1 GTPase activity to prevent organelle scission.