Mitochondria Fusion and Fission

Abstract Mitochondrial structural dynamics is regulated by the fusion or fission of these organelles. Recently published evidence indicates the vital role of mitochondrial fusion and fission in cellular physiology, including progression of apoptosis. These reports indicate that in addition to intimate link between mitochondrial morphogenesis machineries and regulation of mitochondrial steps in apoptosis, certain proteins vital for the regulation of mitochondrial steps in apoptosis can also regulate mitochondrial fusion and fission in healthy cells. In this article, we focus on the regulation of mitochondrial network dynamics. The emerging evidence indicating that proteins implicated in mitochondrial network dynamics are vital for the mitochondrial steps in apoptosis is presented here, as well. Furthermore, the data demonstrating an unexpected role for the B‐cell lymphoma (Bcl)‐2 family members in the regulation of mitochondrial morphogenesis are also discussed. Key concepts: In healthy cells, mitochondrial cycle between several shapes, their morphology result from the equilibrium between mitochondrial fusion and fission. The unique feature of mitochondrial fusion is the necessity of merging double membrane systems from the two fusing mitochondria. This process is mediated by the outer mitochondrial membrane‐associated mitofusin proteins (Mfn1 and Mfn2), and the inner mitochondrial membrane‐associated Opa1. Regulation of mitochondrial fusion and fission has a significant impact on cell viability and early development. The mitochondrial fragmentation occurs concomitantly with the outer mitochondrial membrane (OMM) permeabilization, a critical step in apoptosis. The cooperation between proteins involved in mitochondrial fusion and fission and Bcl‐2 family proteins during apoptosis suggests that changes in mitochondrial network dynamics contribute to apoptotic signalling. The mechanistic link between the core mitochondrial fusion and fission regulating proteins (e.g. Drp1, Mfn2 and Opa1) and proteins from Bcl‐2 family, suggest that Bcl‐2 family proteins also regulate mitochondrial dynamics in healthy cells.