Molecular Machinery and Pathophysiology of Mitochondrial Dynamics

Abstract

Mitochondria are double-membraned organelles that exhibit fluidity. They are the main site of cellular aerobic respiration, providing energy for cell proliferation, migration, and survival; hence, they are called “powerhouses.” Mitochondria play an important role in biological processes such as cell death, cell senescence, autophagy, lipid synthesis, calcium homeostasis, and iron balance. Fission and fusion are active processes that require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and interface proteins that regulate the interaction of these mechanical proteins with organelles. This review discusses the molecular mechanisms of mitochondrial fusion, fission, and physiopathology, emphasizing the biological significance of mitochondrial morphology and dynamics. In particular, the regulatory mechanisms of mitochondria-related genes and proteins in animal cells are discussed, as well as research trends in mitochondrial dynamics, providing a theoretical reference for future mitochondrial research.

Mitochondria-Shaping Proteins and Chemotherapy

“…Following outer membrane fusion, OPA1 is proteolytically hydrolyzed by two endosomal peptidases: Oma1 and the i-AAA protease Yme1l to create two active forms. Long L-OPA1, which is anchored to the mitochondrial inner membrane, and soluble short S-OPA1, which is located at the mitochondrial intermembrane space ( 32 ). IMMs fusion is completed by the combined action of L-OPA1 and S-OPA1 ( 47 ).…”

Plasmodium infection suppresses colon cancer growth by inhibiting proliferation and promoting apoptosis associated with disrupting mitochondrial biogenesis and mitophagy in mice

“…Mitochondrion, a subcellular organelle which plays a major role in cell energy control and metabolism, is essential for the survival and growth of cells [ 53 , 54 ]. As an important regulator involved in the pathways of mitochondrial biogenesis, mitophagy, carcinogenesis, and tumor cell death, including mitochondria-mediated apoptosis, mitochondria have been considered as potential therapeutic targets for cancer [ 55 ].…”

Simple to Complex: The Role of Actin and Microtubules in Mitochondrial Dynamics in Amoeba, Yeast, and Mammalian Cells

“…For example, as reviewed by Madan et al, loss of fission is thought to maintain the undifferentiated state of a cell, while an increase in fusion increases ATP potential and the polarization of hepatocytes [ 25 ]. Cells under starvation conditions will increase fusion and decrease fission to increase their ATP potential [ 24 ]. This is supported by the fact that diabetic and obese patient pancreatic cells have fragmented mitochondria [ 24 ].…”

“…Cells under starvation conditions will increase fusion and decrease fission to increase their ATP potential [ 24 ]. This is supported by the fact that diabetic and obese patient pancreatic cells have fragmented mitochondria [ 24 ]. Additionally, there is extensive remodeling of mitochondria during embryogenesis and mutations within fission and fusion proteins result in developmental defects, some of which are lethal [ 25 ].…”

“…Fission increases are also seen with increased levels of Reactive Oxygen Species (ROS) [ 19 ], though in some organisms, such as the social amoeba Dictyostelium discoideum , the form of ROS determines the effect on both fission and fusion rates [ 20 ]. Fusion increases in response to cellular starvation in an effort to increase mitochondrial respiration and to mediate mitochondrial DNA damage [ 21 , 22 , 23 , 24 ]. It is clear that mitochondrial function and structure are intertwined and that both function and structure regulate cellular processes such as migration, cell division, embryogenesis, and disease [ 25 ].…”