Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles (#618)

Su-Jin kim 1 , Sehyun Chae 2 , Young Do Koo 3 , Hokeun Kim 1 , Byung Yong Ahn 3 , Daehee Hwang 2 , Kyong Soo Park 3 , Sang-Won Lee 1
  1. Department of Chemistry, Center for Proteogenome Research, Korea University, Seoul, Republic of Korea
  2. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea
  3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

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.


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)