Show simple item record

dc.contributor.authorByrne, JJ
dc.contributor.authorSoh, MS
dc.contributor.authorChandhok, G
dc.contributor.authorVijayaraghavan, T
dc.contributor.authorTeoh, J-S
dc.contributor.authorCrawford, S
dc.contributor.authorCobham, AE
dc.contributor.authorYapa, NMB
dc.contributor.authorMirth, CK
dc.contributor.authorNeumann, B
dc.date.accessioned2021-10-12T00:39:40Z
dc.date.available2021-10-12T00:39:40Z
dc.date.issued2019-05
dc.identifierpii: 10.1007/s00018-019-03024-5
dc.identifier.citationByrne, J. J., Soh, M. S., Chandhok, G., Vijayaraghavan, T., Teoh, J. -S., Crawford, S., Cobham, A. E., Yapa, N. M. B., Mirth, C. K. & Neumann, B. (2019). Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.. Cell Mol Life Sci, 76 (10), pp.1967-1985. https://doi.org/10.1007/s00018-019-03024-5.
dc.identifier.issn1420-682X
dc.identifier.urihttp://hdl.handle.net/11343/287516
dc.description.abstractMitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans. Using these techniques, we uncover surprising tissue-specific differences in mitochondrial morphology when fusion or fission proteins are absent. From ultrastructural analysis, we reveal a novel role for the fusion protein FZO-1/mitofusin 2 in regulating the structure of the inner mitochondrial membrane. Moreover, we have determined the influence of the individual mitochondrial fission (DRP-1/DRP1) and fusion (FZO-1/mitofusin 1,2; EAT-3/OPA1) proteins on animal behaviour and lifespan. We show that loss of these mitochondrial fusion or fission regulators induced age-dependent and progressive deficits in animal movement, as well as in muscle and neuronal function. Our results reveal that disruption of fusion induces more profound defects than lack of fission on animal behaviour and tissue function, and imply that while fusion is required throughout life, fission is more important later in life likely to combat ageing-associated stressors. Furthermore, our data demonstrate that mitochondrial function is not strictly dependent on morphology, with no correlation found between morphological changes and behavioural defects. Surprisingly, we find that disruption of either mitochondrial fission or fusion significantly reduces median lifespan, but maximal lifespan is unchanged, demonstrating that mitochondrial dynamics play an important role in limiting variance in longevity across isogenic populations. Overall, our study provides important new insights into the central role of mitochondrial dynamics in maintaining organismal health.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDisruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.
dc.typeJournal Article
dc.identifier.doi10.1007/s00018-019-03024-5
melbourne.affiliation.departmentVeterinary Biosciences
melbourne.affiliation.facultyVeterinary and Agricultural Sciences
melbourne.source.titleCellular and Molecular Life Sciences
melbourne.source.volume76
melbourne.source.issue10
melbourne.source.pages1967-1985
dc.rights.licenseCC BY
melbourne.elementsid1563316
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478650
melbourne.contributor.authorByrne, Joseph
dc.identifier.eissn1420-9071
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record