Journal
NUCLEIC ACIDS RESEARCH
Volume 39, Issue 12, Pages 5098-5108Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkr052
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Funding
- Medical Research Council
- European Union
- Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Heart
- Chang Gung Memorial Hospital, Lin-Kou, Taiwan [CMRPG360491-2, 380651, NSC 97-2321-B-182A-002-MY2]
- MRC [MC_U105663140, MC_U105663148] Funding Source: UKRI
- Medical Research Council [MC_U105663140, MC_U105663148] Funding Source: researchfish
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Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and beta-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of beta-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some beta-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance.
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