Authors:	Wolf, Christina López del Amo, Víctor Arndt, Sabine Bueno, Diones Tenzer, Stefan Hanschmann, Eva-Maria Berndt, Carsten Methner, Axel
Title:	Redox modifications of proteins of the mitochondrial fusion and fission machinery
Online publication date:	27-Aug-2020
Year of first publication:	2020
Language:	english
Abstract:	Mitochondrial fusion and fission tailors the mitochondrial shape to changes in cellular homeostasis. Players of this process are the mitofusins, which regulate fusion of the outer mitochondrial membrane, and the fission protein DRP1. Upon specific stimuli, DRP1 translocates to the mitochondria, where it interacts with its receptors FIS1, MFF, and MID49/51. Another fission factor of clinical relevance is GDAP1. Here, we identify and discuss cysteine residues of these proteins that are conserved in phylogenetically distant organisms and which represent potential sites of posttranslational redox modifications. We reveal that worms and flies possess only a single mitofusin, which in vertebrates diverged into MFN1 and MFN2. All mitofusins contain four conserved cysteines in addition to cysteine 684 in MFN2, a site involved in mitochondrial hyperfusion. DRP1 and FIS1 are also evolutionarily conserved but only DRP1 contains four conserved cysteine residues besides cysteine 644, a specific site of nitrosylation. MFF and MID49/51 are only present in the vertebrate lineage. GDAP1 is missing in the nematode genome and contains no conserved cysteine residues. Our analysis suggests that the function of the evolutionarily oldest proteins of the mitochondrial fusion and fission machinery, the mitofusins and DRP1 but not FIS1, might be altered by redox modifications. Keywords: mitochondria; fusion; fission; redox; metabolism; thiol switch
DDC:	570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5090
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Cells 9 4
Pages or article number:	815
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2020
ISSN:	2073-4409
Publisher URL:	https://doi.org/10.3390/cells9040815
Publisher DOI:	10.3390/cells9040815
Appears in collections:	JGU-Publikationen