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Ahola, S.* ; Pazurek, L.A.* ; Mayer, F.* ; Lampe, P.* ; Hermans, S.* ; Becker, L. ; Amarie, O.V. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Riedel, D.* ; Nolte, H.* ; Langer, T.*

Opa1 processing is dispensable in mouse development but is protective in mitochondrial cardiomyopathy.

Sci. Adv. 10:eadp0443 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mitochondrial fusion and fission accompany adaptive responses to stress and altered metabolic demands. Inner membrane fusion and cristae morphogenesis depends on optic atrophy 1 (Opa1), which is expressed in different isoforms and is cleaved from a membrane-bound, long to a soluble, short form. Here, we have analyzed the physiological role of Opa1 isoforms and Opa1 processing by generating mouse lines expressing only one cleavable Opa1 isoform or a non-cleavable variant thereof. Our results show that expression of a single cleavable or non-cleavable Opa1 isoform preserves embryonic development and the health of adult mice. Opa1 processing is dispensable under metabolic and thermal stress but prolongs life span and protects against mitochondrial cardiomyopathy in OXPHOS-deficient Cox10-/- mice. Mechanistically, loss of Opa1 processing disturbs the balance between mitochondrial biogenesis and mitophagy, suppressing cardiac hypertrophic growth in Cox10-/- hearts. Our results highlight the critical regulatory role of Opa1 processing, mitochondrial dynamics, and metabolism for cardiac hypertrophy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dynamin-related Gtpase; Fusion; Protease; Biogenesis; Extraction; Expression; Morphology; Isoforms; Mutation; Hearts
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 10, Heft: 31, Seiten: , Artikelnummer: eadp0443 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen German center for diabetes Research (dZd)
German Federal Ministry of education and Research
German Research Foundation)
Deutsche Forschungsgemeinschaft (DFG