Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis
Abstract
:1. Introduction
2. Structure and Functions of Mitochondria and Mitochondrial Genome
3. Mechanisms of Mitochondrial Dysfunction
4. Mitochondrial Turnover as Protective Mechanism
5. Mutations of mtDNA Associated with Mitochondrial Dysfunction
6. Directions for Mitochondrial Therapy Development
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Gene Function | Cellular Phenotype | Cristae Abnormalities | Mitochondrial DNA/Nucleoid Aberrancy | Ref. |
---|---|---|---|---|---|
MFN1 MFN2 MFN1+MFN2 | OMM fusion; MFN2 key regulator of the mitochondria-ER contact sites tethering; MFN1; involved in the OPA1-dependent IMM fusion | Reduced cell growth and oxygen consumption, loss of transmembrane potential | Sparse cristae with swollen, fragmented mitochondria with reduced COX activity | Loss of mtDNA (DKO MFN1 and MFN2) and loss of nucleotide (КО, DKO) | [58,59] |
OPA1 | IMM fusion | Loss of transmembrane potential (mammalian cell lines); reduced body weight, muscle atrophy and weakness, kyphosis and hair greying (inducible conditional deletion in skeletal muscle) | Crystae p-depletion, dilation, disorganization | mtDNA loss | [60,61,62] |
MSTO1 | cytosolic mitochondrial fusion regulator | Fragmented mitochondrial network, Enlarged lysosomes | - | Nucleoid clumping segregation of mtDNA; reduced mtDNA copy number | [63] |
RP1 | OMM fission | Delayed apoptosis, reduced membrane potential and ATP synthesis | Densly packed cristae (mito-bulbs) | Nucleoid clustering | [64,65] |
MFF | OMM fission | Premature death, cardiomyopathy | Vacuolated mitochondria with malformed cristae | mtDNA levels decline | [66] |
MIC60 | CJs formation and assembly | Impaired mitochondrial dynamics | Loss of CJs leading to cristae separated from the IBM | Increased nucleoids, decreased transcription of mtDNA-encoded genes | [67] |
Gene | OMIM | Phenotype | Inheritance |
---|---|---|---|
Fusion genes | |||
MFN2 | 608507 | Charcot–Marie–Tooth disease type 2A | AD/AR |
Hereditary motor and sensory neuropathy VIA | AD | ||
ОРА1 | 605290 | Optic atrophy 1 | AD |
Optic atrophy plus syndrome | AD | ||
Behr syndrome | AR | ||
Fission genes | |||
DNM1L | 603850 | Encephalopathy | AR/AD |
Optic atrophy 5 | AD | ||
MFF | 614785 | Encephalopathy | AR |
MIEF2 | 615498 | Mitochondrial myopathy | AR |
DNM2 | 602378 | Centronuclear myopathy 1 | AD |
Charcot–Marie–Tooth disease, axonal type 2M | AD | ||
Charcot–Marie–Tooth disease, dominant intermediate B | AD | ||
Lethal congenital contracture syndrome 5 | AR | ||
INF2 | 610982 | Charcot–Marie–Tooth disease type E | AD |
Focal segmental glomerulosclerosis | AD | ||
genes-regulators of mitochondrial dynamics | |||
MSTO1 | 617619 | Myopathy and ataxia | AR/AD |
SLC25A46 | 610826 | Pontocerebellar hypoplasia type 1 | AR |
Hereditary sensory motor neuropathy | AR | ||
Optic atrophy spectrum disorders | AR | ||
GDAP1 | 606598 | Charcot–Marie–Tooth disease type 4A | AR |
Charcot–Marie–Tooth disease type 2K | AR/AD | ||
Charcot–Marie–Tooth disease type A | AR | ||
Charcot–Marie–Tooth disease with vocal cord paresis | AR |
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Markin, A.M.; Khotina, V.A.; Zabudskaya, X.G.; Bogatyreva, A.I.; Starodubova, A.V.; Ivanova, E.; Nikiforov, N.G.; Orekhov, A.N. Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis. Life 2021, 11, 165. https://doi.org/10.3390/life11020165
Markin AM, Khotina VA, Zabudskaya XG, Bogatyreva AI, Starodubova AV, Ivanova E, Nikiforov NG, Orekhov AN. Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis. Life. 2021; 11(2):165. https://doi.org/10.3390/life11020165
Chicago/Turabian StyleMarkin, Alexander M., Viktoria A. Khotina, Xenia G. Zabudskaya, Anastasia I. Bogatyreva, Antonina V. Starodubova, Ekaterina Ivanova, Nikita G. Nikiforov, and Alexander N. Orekhov. 2021. "Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis" Life 11, no. 2: 165. https://doi.org/10.3390/life11020165