Review
New insights into the function and regulation of mitochondrial fission

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Abstract

Mitochondrial morphology changes dynamically by coordinated fusion and fission and cytoskeleton-based transport. Cycles of outer and inner membrane fusion and fission are required for the exchange of damaged mitochondrial genome DNA, proteins, and lipids with those of healthy mitochondria to maintain robust mitochondrial structure and function. These dynamics are crucial for cellular life and death, because they are essential for cellular development and homeostasis, as well as apoptosis. Disruption of these functions leads to cellular dysfunction, resulting in neurologic disorders and metabolic diseases. The cytoplasmic dynamin-related GTPase Drp1 plays a key role in mitochondrial fission, while Mfn1, Mfn2 and Opa1 are involved in fusion reaction. Here, we review current knowledge regarding the regulation and physiologic relevance of Drp1-dependent mitochondrial fission: the initial recruitment and assembly of Drp1 on the mitochondrial fission foci, regulation of Drp1 activity by post-translational modifications, and the role of mitochondrial fission in cell pathophysiology.

Highlights

► Mitochondrial morphology is controlled by fusion and fission. ► Dynamin-related protein 1 (Drp1) mediates mitochondrial fission. ► Mitochondrial fission plays an important role in apoptosis and mitochondrial quality control. ► Drp1 is regulated by various post-translational modifications. ► Mitochondrial fission deficiencies cause various human diseases.

Abbreviations

AKAP1
A kinase anchoring protein 1
Endo B1
endophilin B1
ER
endoplasmic reticulum
GDAP1
ganglioside-induced differentiation-associated protein 1
GED
GTPase effector domain
GFP
green fluorescent protein
KO
knockout
LRRK2
leucine-rich repeat kinase 2
MEF
mouse embryonic fibroblast
Mff
mitochondrial fission factor
MiD51
mitochondrial dynamics 51
MIEF1
mitochondrial elongation factor 1
MIM
mitochondrial inner membrane
Mfn2
mitofusin 2
MOM
mitochondrial outer membrane
NO
nitric oxide
PKA
cAMP-dependent protein kinase
RNAi
RNA interference
SUMO
small ubiquitin-like modifier
VD
variable domain

Keywords

Mitochondrial fission
Drp1
Apoptosis
Mitophagy
Post-translational modification
Neurodegenerative disease

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