RRC ID 55036
著者 Byrne JJ, Soh MS, Chandhok G, Vijayaraghavan T, Teoh JS, Crawford S, Cobham AE, Yapa NMB, Mirth CK, Neumann B.
タイトル Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.
ジャーナル Cell Mol Life Sci
Abstract Mitochondria 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.
巻・号 76(10)
ページ 1967-1985
公開日 2019-5-1
DOI 10.1007/s00018-019-03024-5
PII 10.1007/s00018-019-03024-5
PMID 30840087
PMC PMC6478650
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Dynamins / genetics Dynamins / metabolism GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Kaplan-Meier Estimate Longevity / genetics* Microscopy, Electron, Transmission Mitochondria / genetics Mitochondria / metabolism Mitochondria / ultrastructure Mitochondria, Muscle / genetics Mitochondria, Muscle / metabolism Mitochondria, Muscle / ultrastructure Mitochondrial Dynamics / genetics* Mitochondrial Proteins / genetics* Mitochondrial Proteins / metabolism Mutation* Neurons / metabolism Neurons / ultrastructure
IF 7.014
引用数 9
リソース情報
線虫 tm1108