A Mitochondrial Proteome Profile Indicative of Type 2 Diabetes Mellitus in Skeletal Muscles

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2018 Sep 30

PMID 30266947

Citations 24

Authors

Sehyun Chae

Su-Jin Kim

Young Do Koo

Jung Hwa Lee

Hokeun Kim

Byung Yong Ahn

Yong-Chan Ha

Yong-Hak Kim

Mi Gyeong Jang

Kyung-Hoi Koo

Sung Hee Choi

Soo Lim

Young Joo Park

Hak Chul Jang

Daehee Hwang

Sang-Won Lee

Kyong Soo Park

Affiliations

Soon will be listed here.

Abstract

The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with mitochondrial functions in insulin-responsive tissues. The mitochondrial proteome, compared with the mitochondrial genome, which only contains 37 genes in humans, can provide more comprehensive information for thousands of mitochondrial proteins regarding T2DM-associated mitochondrial functions. However, T2DM-associated protein signatures in insulin-responsive tissues are still unclear. Here, we performed extensive proteome profiling of mitochondria from skeletal muscles in nine T2DM patients and nine nondiabetic controls. A comparison of the mitochondrial proteomes identified 335 differentially expressed proteins (DEPs) between T2DM and nondiabetic samples. Functional and network analyses of the DEPs showed that mitochondrial metabolic processes were downregulated and mitochondria-associated ER membrane (MAM) processes were upregulated. Of the DEPs, we selected two (NDUFS3 and COX2) for downregulated oxidative phosphorylation and three (CALR, SORT, and RAB1A) for upregulated calcium and protein transport as representative mitochondrial and MAM processes, respectively, and then confirmed their differential expression in independent mouse and human samples. Therefore, we propose that these five proteins be used as a potential protein profile that is indicative of the dysregulation of mitochondrial functions in T2DM, representing downregulated oxidative phosphorylation and upregulated MAM functions.

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