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Duvezin-Caubet, S.* ; Koppen, M.* ; Wagener, J.* ; Zick, M.* ; Israel, L.* ; Bernacchia, A.* ; Jagasia, R. ; Rugarli, E.I.* ; Imhof, A.* ; Neupert, W.* ; Langer, T.* ; Reichert, A.S.*

OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria.

Mol. Biol. Cell 18, 3582-3590 (2007)
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The morphology of mitochondria in mammalian cells is regulated by proteolytic cleavage of OPA1, a dynamin-like GTPase of the mitochondrial inner membrane. The mitochondrial rhomboid protease PARL, and paraplegin, a subunit of the ATP-dependent m-AAA protease, were proposed to be involved in this process. Here, we characterized individual OPA1 isoforms by mass spectrometry, and we reconstituted their processing in yeast to identify proteases involved in OPA1 cleavage. The yeast homologue of OPA1, Mgm1, was processed both by PARL and its yeast homologue Pcp1. Neither of these rhomboid proteases cleaved OPA1. The formation of small OPA1 isoforms was impaired in yeast cells lacking the m-AAA protease subunits Yta10 and Yta12 and was restored upon expression of murine or human m-AAA proteases. OPA1 processing depended on the subunit composition of mammalian m-AAA proteases. Homo-oligomeric m-AAA protease complexes composed of murine Afg3l1, Afg3l2, or human AFG3L2 subunits cleaved OPA1 with higher efficiency than paraplegin-containing m-AAA proteases. OPA1 processing proceeded normally in murine cell lines lacking paraplegin or PARL. Our results provide evidence for different substrate specificities of m-AAA proteases composed of different subunits and reveal a striking evolutionary switch of proteases involved in the proteolytic processing of dynamin-like GTPases in mitochondria.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 1059-1524
e-ISSN 1939-4586
Zeitschrift Molecular Biology of the Cell
Quellenangaben Band: 18, Heft: 9, Seiten: 3582-3590 Artikelnummer: , Supplement: ,
Verlag American Society for Cell Biology (ASCB)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)