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Cell Biol Int. 2019 Nov 27. doi: 10.1002/cbin.11274. [Epub ahead of print]

Melatonin reverses the oxidative stress and mitochondrial dysfunction caused by LETM1 silencing.

Author information

1
Department of Molecular Biology and Genetics, Faculty of Science and Arts, Namık Kemal University, 59030, Tekirdağ, Turkey.

Abstract

LETM1 is a mitochondrial inner-membrane protein, which is encoded by a gene present in a locus of 4p, which, in turn, is deleted in the Wolf-Hirschhorn Syndrome, and is assumed to be related to its pathogenesis. The cellular damage caused by the deletion is presumably related to oxidative stress. Melatonin has many beneficial roles in protecting mitochondria by scavenging reactive oxygen species, maintaining membrane potential, and improving functions. The aim of this study was to investigate the effects of melatonin administration to LETM1-silenced mouse embryonic fibroblast cells as a cellular model for LETM1 deficiency. We transfected mouse embryonic fibroblast cells with a pair of siRNA against LETM1 and monitored the oxidative stress and mitochondrial functions with or without melatonin addition. MnSOD expression and aconitase activity decreased and oxidized protein levels increased in LETM1-silenced cells. LETM1 suppression did not alter the expression of OXPHOS complexes, but the oxygen consumption rates decreased significantly; however, this change was not related to complex I but instead involved complex IV and complex II. Melatonin supplementation effectively normalized the parameters studied, including the oxygen consumption rate. Our findings identified a novel effect of LETM1 deficiency on cellular respiration via complex II as well as a potential beneficial role of melatonin treatment. On the other hand, these effects may be specific to the cell line used and need to be verified in other cell lines.

KEYWORDS:

LETM1; MnSOD; Wolf-Hirschhorn Syndrome; melatonin; oxidative phosphorylation complexes; oxidative stress

PMID:
31777134
DOI:
10.1002/cbin.11274

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