Question

Briefly outline the processes of mitochondrial fission and fusion; and how dysregulation or disruption of these mechanisms can contribute to disease

Answer 1

Mitochondrial fission and fusion are very dynamic processes which maintain cellular homeostasis and thus regualte optimum function of the heart. In this regard, following pathways for fission and fusion have been explained, with special relevance to clinical disorders:

Mitochondrial fission: The fission or splitting of mitochondria is maintained by the non-canonical Wnt mediated Bcl-Drp1 pathway. Up-regulation of these molecular regulators lead to enhanced fission of mitochondria. Studies have shown that dys-regulation (appropriately, up-regulation) of fission is directly associated with pathologies of the myocardium including ischemic heart disease, hypoxic heart, idiopathic cardiomyopathy.

Mitochondrial fusion: Mitochondrial fusion is a less frequent phenomenon but does takes place under the surveillance of Opa-1/NM23-H4 pathway. Studies have shown that mitochondrial fusion is inseparably associated with cytochrome-c release, leading to caspase-3,-7 activation and apoptosis. Thus, the cases of myocardial infarction are usually associated with mitochondrial fusion.