Actin and myosin contribute to mammalian mitochondrial DNA maintenance.

TitleActin and myosin contribute to mammalian mitochondrial DNA maintenance.
Publication TypeJournal Article
Year of Publication2011
AuthorsReyes, A, He, J, Mao, CC, Bailey, LJ, Di Re, M, Sembongi, H, Kazak, L, Dzionek, K, Holmes, JB, Cluett, TJ, Harbour, ME, Fearnley, IM, Crouch, RJ, Conti, MA, Adelstein, RS, Walker, JE, Holt, IJ
JournalNucleic Acids Res
Volume39
Issue12
Pagination5098-108
Date Published2011 Jul
ISSN1362-4962
KeywordsActins, Animals, Cells, Cultured, DNA, Mitochondrial, Gene Silencing, Humans, Mice, Mitochondria, Mitochondrial Proteins, Myosin Heavy Chains, Nonmuscle Myosin Type IIA, Nonmuscle Myosin Type IIB, Rats
Abstract

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 β-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 β-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some β-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.

DOI10.1093/nar/gkr052
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkr052
PubMed ID21398640
PubMed Central IDPMC3130256
Grant ListMC_U105663140 / / Medical Research Council / United Kingdom
MC_U105663148 / / Medical Research Council / United Kingdom
/ / Intramural NIH HHS / United States