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 journalArticle

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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
Number of pages1
JournalExperimental & molecular medicine
Volume50
Issue number9
DOIs
Publication statusPublished - 2018 Sep 28

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Proteome
Medical problems
Type 2 Diabetes Mellitus
Muscle
Skeletal Muscle
Mitochondria
Proteins
Down-Regulation
Mitochondrial Proteins
Oxidative Phosphorylation
Membranes
Genes
Insulin
Tissue
Mitochondrial Genome
Protein Transport
Calcium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles. / Chae, Sehyun; Kim, Su Jin; Do Koo, Young; Lee, Jung Hwa; Kim, Hokeun; Ahn, Byung Yong; Ha, Yong Chan; Kim, Yong Hak; Jang, Mi Gyeong; Koo, Kyung Hoi; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Jang, Hak Chul; Hwang, Daehee; Lee, Sang-Won; Park, Kyong Soo.

In: Experimental & molecular medicine, Vol. 50, No. 9, 28.09.2018.

Research output: Contribution to journalArticle

Chae, S, Kim, SJ, Do Koo, Y, Lee, JH, Kim, H, Ahn, BY, Ha, YC, Kim, YH, Jang, MG, Koo, KH, Choi, SH, Lim, S, Park, YJ, Jang, HC, Hwang, D, Lee, S-W & Park, KS 2018, 'A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles', Experimental & molecular medicine, vol. 50, no. 9. https://doi.org/10.1038/s12276-018-0154-6
Chae, Sehyun ; Kim, Su Jin ; Do Koo, Young ; Lee, Jung Hwa ; Kim, Hokeun ; Ahn, Byung Yong ; Ha, Yong Chan ; Kim, Yong Hak ; Jang, Mi Gyeong ; Koo, Kyung Hoi ; Choi, Sung Hee ; Lim, Soo ; Park, Young Joo ; Jang, Hak Chul ; Hwang, Daehee ; Lee, Sang-Won ; Park, Kyong Soo. / A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles. In: Experimental & molecular medicine. 2018 ; Vol. 50, No. 9.
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AU - Ha, Yong Chan

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AU - Choi, Sung Hee

AU - Lim, Soo

AU - Park, Young Joo

AU - Jang, Hak Chul

AU - Hwang, Daehee

AU - Lee, Sang-Won

AU - Park, Kyong Soo

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N2 - 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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