Association of mitochondria with microtubules inhibits mitochondrial fission by precluding assembly of the fission protein Dnm1.
J Biol Chem
; 294(10): 3385-3396, 2019 03 08.
Article
em En
| MEDLINE
| ID: mdl-30602572
ABSTRACT
Mitochondria are organized as tubular networks in the cell and undergo fission and fusion. Although several of the molecular players involved in mediating mitochondrial dynamics have been identified, the precise cellular cues that initiate mitochondrial fission or fusion remain largely unknown. In fission yeast (Schizosaccharomyces pombe), mitochondria are organized along microtubule bundles. Here, we employed deletions of kinesin-like proteins to perturb microtubule dynamics and used high-resolution and time-lapse fluorescence microscopy, revealing that mitochondrial lengths mimic microtubule lengths. Furthermore, we determined that compared with WT cells, mutant cells with long microtubules exhibit fewer mitochondria, and mutant cells with short microtubules have an increased number of mitochondria because of reduced mitochondrial fission in the former and elevated fission in the latter. Correspondingly, upon onset of closed mitosis in fission yeast, wherein interphase microtubules assemble to form the spindle within the nucleus, we observed increased mitochondrial fission. We found that the consequent rise in the mitochondrial copy number is necessary to reduce partitioning errors during independent segregation of mitochondria between daughter cells. We also discovered that the association of mitochondria with microtubules physically impedes the assembly of the fission protein Dnm1 around mitochondria, resulting in inhibition of mitochondrial fission. Taken together, we demonstrate a mechanism for the regulation of mitochondrial fission that is dictated by the interaction between mitochondria and the microtubule cytoskeleton.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Schizosaccharomyces
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Proteínas de Schizosaccharomyces pombe
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Dinaminas
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Dinâmica Mitocondrial
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Microtúbulos
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Mitocôndrias
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia