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- W2692479174 abstract "OPA1 is a GTPase that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In humans, eight isoforms are expressed as combinations of long and short forms, but it is unclear whether OPA1 functions are associated with specific isoforms and/or domains. To address this, we expressed each of the eight isoforms or different constructs of isoform 1 in Opa1-/- MEFs. We observed that any isoform could restore cristae structure, mtDNA abundance, and energetic efficiency independently of mitochondrial network morphology. Long forms supported mitochondrial fusion; short forms were better able to restore energetic efficiency. The complete rescue of mitochondrial network morphology required a balance of long and short forms of at least two isoforms, as shown by combinatorial isoform silencing and co-expression experiments. Thus, multiple OPA1 isoforms are required for mitochondrial dynamics, while any single isoform can support all other functions. These findings will be useful in designing gene therapies for patients with OPA1 haploinsufficiency." @default.
- W2692479174 created "2017-06-30" @default.
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- W2692479174 date "2017-06-01" @default.
- W2692479174 modified "2023-10-14" @default.
- W2692479174 title "OPA1 Isoforms in the Hierarchical Organization of Mitochondrial Functions" @default.
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- W2692479174 doi "https://doi.org/10.1016/j.celrep.2017.05.073" @default.
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