The thiol switch C684 in Mitofusin-2 mediates redox-induced alterations of mitochondrial shape and respiration

Neurochemistry International
Osamah ThaherAxel Methner

Abstract

Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated. We now studied mitochondrial function using high-resolution respirometry in cells stably expressing wildtype or C684A MFN2 in MFN2-deficient fibroblasts in response to alterations of the redox state. Empty vector and untransfected cells served as controls. A single treatment of cells with 100 μM hydrogen peroxide 24 h before analysis had no effect on wildtype cells, but normalized the otherwise increased respiration of knockout cells and significantly increased respiration in C684A cells. In line with this, treating per...Continue Reading

Citations

Jan 11, 2018·Antioxidants·Adam J TrewinAndrew P Wojtovich
Apr 1, 2018·Arhiv za higijenu rada i toksikologiju·Kristina Dominko, Domagoj Đikić
Dec 8, 2017·The Journal of Cell Biology·Sevan MattieHeidi M McBride
Sep 5, 2017·Frontiers in Oncology·Maria Livia SassanoPatrizia Agostinis
Jul 22, 2018·Essays in Biochemistry·Lisa TilokaniJulien Prudent
Mar 26, 2021·Frontiers in Physiology·Ava LiaghatiMary-Ellen Harper
Apr 27, 2021·Antioxidants & Redox Signaling·Masuko Ushio-FukaiTohru Fukai
Oct 30, 2020·Current Medicinal Chemistry·Marcos Martínez-Banaclocha
Jul 24, 2021·EMBO Reports·Sergi Casellas-DíazFrancesc X Soriano

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