Reciprocal Regulation of Mitochondrial Fission and Fusion

Mitochondria are dynamic organelles constantly undergoing fusion and fission events. The morphology of the mitochondrial network is determined by the balance between fusion and fission events. Changes in mitochondrial morphology facilitate the integration of mitochondrial function with physiological changes in the cell. Hyperfused mitochondrial networks can be due to increased fusion and/or decreased fission. Fragmented mitochondrial networks can be a result of either more fission and/or reduced fusion. An emerging trend in mitochondrial network remodeling is the reciprocal regulation of fission and fusion, where regulatory pathways influence both processes. The dynamic processes of mitochondrial fission and fusion are tightly regulated, determine mitochondrial shape, and influence mitochondrial functions. For example, fission and fusion mediate energy output, production of reactive oxygen species (ROS), and mitochondrial quality control. As our understanding of the molecular machinery and mechanisms regulating dynamic changes in the mitochondrial network continues to grow, we are beginning to unravel important signaling pathways that integrate physiological cues to modulate mitochondrial morphology and function. Here, we highlight reciprocal regulation of mitochondrial fusion and fission as an emerging trend in the regulation of mitochondrial function. The dynamic processes of mitochondrial fission and fusion are tightly regulated, determine mitochondrial shape, and influence mitochondrial functions. For example, fission and fusion mediate energy output, production of reactive oxygen species (ROS), and mitochondrial quality control. As our understanding of the molecular machinery and mechanisms regulating dynamic changes in the mitochondrial network continues to grow, we are beginning to unravel important signaling pathways that integrate physiological cues to modulate mitochondrial morphology and function. Here, we highlight reciprocal regulation of mitochondrial fusion and fission as an emerging trend in the regulation of mitochondrial function. proteolytic core of the proteasome, which can degrade oxidized proteins and proteins with intrinsically unstructured domains in a ubiquitin-independent manner. comprises the 20S proteolytic core, responsible for degrading proteins, which is capped with the 19S regulatory complex, responsible for recognizing ubiquitinated substrates. PTM that involves the addition of an acetyl group to specific lysine residues on target proteins. nonbilayer-forming mitochondrial phospholipid found primarily in the IMM. mitochondrial inner membrane invaginations; remodeling cristae morphology influences mitochondrial energetic output and susceptibility to apoptosis. mitochondrial genome; 16.6 kb circular genome present in 100–1000 copies per cell, encoding 13 mitochondrial proteins, two mitochondrial ribosomal RNAs, and 22 transfer RNAs. removal of dysfunctional mitochondria via autophagy. PTM that is dependent on nutrient availability and involves the addition of O-GlcNAc to target proteins by O-GlcNAc transferase. an oxidative environment that is the result increased production or accumulation of ROS. nonbilayer-forming phospholipid that promotes membrane curvature; important CL precursor. PTM that involves the reversible addition of phosphate to tyrosine, threonine, or serine residues on target proteins by a protein kinase. highly reactive compounds produced during mitochondrial respiration, such as superoxide, hydrogen peroxide, and hydroxyl radicals; ROS are important for retrograde cellular signaling; however, high levels of ROS can damage proteins, DNA, and lipids. mode of cellular communication where ROS propagate important information that modulates cellular function. formation of cytoprotective hyperfused mitochondrial networks in response to acute stress stimuli (e.g., oxidative stress, cycloheximide, UV irradiation, and nutrient starvation). PTM that involves addition of small ubiquitin-like modifier (SUMO) moieties to target proteins by SUMO ligases; SUMO modifications can promote protein stability and functional interactions. PTM that involves covalent addition of ubiquitin (Ub) (a 76-amino acid polypeptide) to specific lysine residues on target proteins by Ub ligases; poly-ub chains typically promote protein degradation by the 26S proteasome, and mono-ub can promote protein–protein interactions.