Abstract
Mitochondria are highly dynamic organelles and important for a variety of cellular functions. They constantly undergo fission and fusion events, referred to as mitochondrial dynamics, which affects the shape, size, and number of mitochondria in the cell, as well as mitochondrial subcellular transport, mitochondrial quality control (mitophagy), and programmed cell death (apoptosis). Dysfunctional mitochondrial dynamics is associated with various human diseases. Mitochondrial dynamics is mediated by a set of mitochondria-shaping proteins in both yeast and mammals. In this review, we describe recent insights into the potential molecular mechanisms underlying mitochondrial fusion and fission, particularly highlighting the coordinating roles of different mitochondria-shaping proteins in the processes, as well as the roles of the endoplasmic reticulum (ER), the actin cytoskeleton and membrane phospholipids in the regulation of mitochondrial dynamics. We particularly focus on emerging roles for the mammalian mitochondrial proteins Fis1, Mff, and MIEFs (MIEF1 and MIEF2) in regulating the recruitment of the cytosolic Drp1 to the surface of mitochondria and how these proteins, especially Fis1, mediate crosstalk between the mitochondrial fission and fusion machineries. In summary, this review provides novel insights into the molecular mechanisms of mammalian mitochondrial dynamics and the involvement of these mechanisms in apoptosis and autophagy.
Highlights
Mitochondria are double membrane-bound organelles present in most eukaryotic cells
We discuss how mitochondrial fusion and fission is regulated by the mitochondria-shaping proteins, and by other co-factors such as the endoplasmic reticulum (ER) and the actin cytoskeleton, as well as how mitochondrial dynamics influences a variety of cellular biological processes such as apoptosis and mitophagy
The mitochondrial fusion machinery characterized in yeast is composed of three key proteins, Fzo1p and Ugo1p, which are anchored in the mitochondrial outer membrane (MOM), and Mgm1p, localized in the mitochondrial inner membrane (MIM) (Figure 1)
Summary
Mitochondria are double membrane-bound organelles present in most eukaryotic cells They are traditionally considered to function as the powerhouses of the cell, generating adenosine triphosphate (ATP) through oxidative phosphorylation, used for cellular chemical energy. Mitochondria have their own genome, known as mitochondrial DNA (mtDNA), which in mammalian cells contains 37 genes that are essential for normal mitochondrial function. A reason why these particular genes are found in the mitochondrial genome is that the encoded proteins are highly hydrophobic and would have a problem entering the mitochondria [1,2,3]. The balance of fission and fusion events is termed mitochondrial dynamics, which is controlled by a number of mitochondria-shaping proteins encoded by genes in the nuclear genome. We discuss how mitochondrial fusion and fission is regulated by the mitochondria-shaping proteins, and by other co-factors such as the endoplasmic reticulum (ER) and the actin cytoskeleton, as well as how mitochondrial dynamics influences a variety of cellular biological processes such as apoptosis and mitophagy
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