OPA1 processing in cell death and disease – the long and short of it
Thomas MacVicar,Thomas Langer +1 more
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TLDR
Proteolytic processing of the dynamin-like GTPase OPA1 is emerging as a crucial regulator of mitochondrial dynamics and quality control, with exciting therapeutic potential in mitochondrial disease.Abstract:
The regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and preserving cellular health. OPA1 governs the delicate balance between fusion and fission in the dynamic mitochondrial network. A disturbance of this balance, often observed under stress and pathologic conditions, causes mitochondrial fragmentation and can ultimately result in cell death. As discussed in this Commentary, these morphological changes are regulated by proteolytic processing of OPA1 by the inner-membrane peptidases YME1L (also known as YME1L1) and OMA1. Long, membrane-bound forms of OPA1 are required for mitochondrial fusion, but their processing to short, soluble forms limits fusion and can facilitate mitochondrial fission. Excessive OPA1 processing by the stress-activated protease OMA1 promotes mitochondrial fragmentation and, if persistent, triggers cell death and tissue degeneration in vivo The prevention of OMA1-mediated OPA1 processing and mitochondrial fragmentation might thus offer exciting therapeutic potential for human diseases associated with mitochondrial dysfunction.read more
Citations
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Mitochondrial dynamics: overview of molecular mechanisms
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References
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TL;DR: In their Perspective, Hoppins and Nunnari explain that the endoplasmic reticulum is an active participant in mitochondrial division and discuss how mitochondrial dynamics and cell death are linked.
Journal ArticleDOI
Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development
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Journal ArticleDOI
ER Tubules Mark Sites of Mitochondrial Division
Jonathan R. Friedman,Laura L. Lackner,Matthew West,Jared R. DiBenedetto,Jodi Nunnari,Gia K. Voeltz +5 more
TL;DR: It was found that mitochondrial division occurred at positions where ER tubules contacted mitochondria and mediated constriction before Drp1 recruitment, suggesting that ERtubules may play an active role in defining the position of mitochondrial division sites.
Journal ArticleDOI
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.
Stephan Züchner,Stephan Züchner,Irina V. Mersiyanova,Maria Muglia,Nisrine Bissar-Tadmouri,Nisrine Bissar-Tadmouri,Julie M. Rochelle,Elena L. Dadali,Mario Zappia,Eva Nelis,Alessandra Patitucci,Jan Senderek,Yesim Parman,Oleg V. Evgrafov,Peter De Jonghe,Yuji Takahashi,Shoij Tsuji,Margaret A. Pericak-Vance,Aldo Quattrone,Esra Battologlu,Alexander V. Polyakov,Vincent Timmerman,J. Michael Schröder,Jeffery M. Vance +23 more
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