Nano-positioning and tubulin conformation contribute to axonal transport regulation of mitochondria along microtubules.

TitleNano-positioning and tubulin conformation contribute to axonal transport regulation of mitochondria along microtubules.
Publication TypeJournal Article
Year of Publication2022
AuthorsVan Steenbergen V, Lavoie-Cardinal F, Kazwiny Y, Decet M, Martens T, Verstreken P, Boesmans W, De Koninck P, Berghe PVanden
JournalProc Natl Acad Sci U S A
Date Published2022 Nov 08
KeywordsAxonal Transport, Axons, Kinesins, Microtubules, Mitochondria, Molecular Conformation, Tubulin

Correct spatiotemporal distribution of organelles and vesicles is crucial for healthy cell functioning and is regulated by intracellular transport mechanisms. Controlled transport of bulky mitochondria is especially important in polarized cells such as neurons that rely on these organelles to locally produce energy and buffer calcium. Mitochondrial transport requires and depends on microtubules that fill much of the available axonal space. How mitochondrial transport is affected by their position within the microtubule bundles is not known. Here, we found that anterograde transport, driven by kinesin motors, is susceptible to the molecular conformation of tubulin in neurons both in vitro and in vivo. Anterograde velocities negatively correlate with the density of elongated tubulin dimers like guanosine triphosphate (GTP)-tubulin. The impact of the tubulin conformation depends primarily on where a mitochondrion is positioned, either within or at the rim of microtubule bundle. Increasing elongated tubulin levels lowers the number of motile anterograde mitochondria within the microtubule bundle and increases anterograde transport speed at the microtubule bundle rim. We demonstrate that the increased kinesin velocity and density on microtubules consisting of elongated dimers add to the increased mitochondrial dynamics. Our work indicates that the molecular conformation of tubulin contributes to the regulation of mitochondrial motility and as such to the local distribution of mitochondria along axons.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID36322761
PubMed Central IDPMC9659393


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Canadian Institutes of Health Research - Instituts de recherche en santé du Canada Fonds de recherche du Québec – Nature et technologies (FRQNT)Fonds de la recherche en santé du Québec   Natural Sciences and Engineering Research Council of Canada (NSERC) - Conseil de recherche en sciences naturelles et en génie du Canada (CRSNG)innovation.caHuman Frontier Science ProgramCanada First Research Excellence FundSentinelle Nord