Universität zu Köln

Vrettou, Sofia and Wirth, Brunhilde ORCID: 0000-0003-4051-5191 (2022). S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases. Int. J. Mol. Sci., 23 (24). BASEL: MDPI. ISSN 1422-0067

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Abstract

Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. However, a growing body of evidence suggests that S-glutathionylation plays a key role in core cell processes, particularly in mitochondria, which are the main source of reactive oxygen species. S-nitrosylation, another post-translational modification, was identified >150 years ago, but it was re-introduced as a prototype cell-signaling mechanism only recently, one that tightly regulates core processes within the cell's sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis. In many neurodegenerative disorders, mitochondria dysfunction and oxidative/nitrosative stresses trigger or exacerbate their pathologies. Despite the substantial amount of research for most of these disorders, there are no successful treatments, while antioxidant supplementation failed in the majority of clinical trials. Herein, we discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and Friedreich's ataxia.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vrettou, Sofia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-662818
DOI:	10.3390/ijms232415849
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	23
Number:	24
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AMYOTROPHIC-LATERAL-SCLEROSIS; ALPHA-KETOGLUTARATE DEHYDROGENASE; MILD COGNITIVE IMPAIRMENT; BRANCHED-CHAIN AMINOTRANSFERASE; PROTEIN DISULFIDE-ISOMERASE; TRANSGENIC MOUSE MODEL; NITRIC-OXIDE SYNTHASE; NEURONAL CELL-DEATH; OXIDATIVE STRESS; REACTIVE OXYGEN Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66281