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Biochem Biophys Res Commun. 2017 Apr 29;486(2):465-469. doi: 10.1016/j.bbrc.2017.03.063. Epub 2017 Mar 16.

ABCB10 depletion reduces unfolded protein response in mitochondria.

Author information

1
Department of Medical Technology, Faculty of Health Sciences, Kumamoto Health Science University, Kumamoto 861-5598, Japan. Electronic address: yano@kumamoto-hsu.ac.jp.

Abstract

Mitochondria have many functions, including ATP generation. The electron transport chain (ETC) and the coupled ATP synthase generate ATP by consuming oxygen. Reactive oxygen species (ROS) are also produced by ETC, and ROS damage deoxyribonucleic acids, membrane lipids and proteins. Recent analysis indicate that mitochondrial unfolded protein response (UPRmt), which enhances expression of mitochondrial chaperones and proteases to remove damaged proteins, is activated when damaged proteins accumulate in the mitochondria. In Caenorhabditis elegans, HAF-1, a putative ortholog of human ABCB10, plays an essential role in signal transduction from mitochondria to nuclei to enhance UPRmt. Therefore, it is possible that ABCB10 has a role similar to that of HAF-1. However, it has not been reported whether ABCB10 is a factor in the signal transduction pathway to enhance UPRmt. In this study, ABCB10 was depleted in HepG2 cells using small interfering RNA (siRNA), and the effect was examined. ABCB10 depletion upregulated ROS and the expression of ROS-detoxifying enzymes (SOD2, GSTA1, and GSTA2), and SESN3, a protein induced by ROS to protect the cell from oxidative stress. In addition, ABCB10 depletion significantly decreased expression of UPRmt-related mitochondrial chaperones (HSPD1 and DNAJA3), and a mitochondrial protease (LONP1). However, the putative activity of ABCB10 to export peptides from mitochondria was not lost by ABCB10 depletion. Altogether, these data suggest that ABCB10 is involved in UPRmt signaling pathway similar to that of HAF-1, although ABCB10 probably does not participate in peptide export from mitochondria.

KEYWORDS:

ABCB10; Mitochondria; Mitochondria unfolded protein response; Redox; Signaling pathway

PMID:
28315685
DOI:
10.1016/j.bbrc.2017.03.063
[Indexed for MEDLINE]

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