A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles

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

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Article number129
JournalExperimental and Molecular Medicine
Volume50
Issue number9
DOIs
Publication statusPublished - 2018 Sept 1

Bibliographical note

Funding Information:
This study was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2017M3C9A5031597) and Institute for Basic Science (IBS-R013-G1) funded by the Korean Ministry of Science, ICT & Future Planning. National Research Foundation grant funded by the Korea government (2006-2005410), and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277).

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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