TY - JOUR
T1 - Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome
AU - Sathe, Gajanan
AU - Deepha, Sekar
AU - Gayathri, Narayanappa
AU - Nagappa, Madhu
AU - Parayil Sankaran, Bindu
AU - Taly, Arun B.
AU - Khanna, Tripti
AU - Pandey, Akhilesh
AU - Govindaraj, Periyasamy
N1 - Funding Information:
The authors thank patient and control subjects for participating in this study. PG acknowledge the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India for financial support. NG was supported by Indian Council of Medical Research (ICMR), Government of India (ICMR Ref No.5/4-5/129/TF/Biobank/2013-NCD-I). AP acknowledge the DBT/Wellcome Trust India Alliance for Margdarshi Fellowship (grant number IA/M/15/1/502023). SD is a recipient of Senior Research Fellowship from ICMR, Government of India.
Publisher Copyright:
© 2021 Elsevier B.V. and Mitochondria Research Society
PY - 2021/5
Y1 - 2021/5
N2 - Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Eighty-six differentially altered proteins were identified, of which thirty-seven mitochondrial proteins were differentially expressed, and most of the proteins (37%) were down-regulated in the OXPHOS complex-IV. Also, nine phosphopeptides that correspond to eight mitochondrial proteins were significantly affected in EE patient. These altered proteins recognized are involved in several pathways and molecular functions, predominantly in oxidoreductase activity. This is the first study that has integrated proteome and phosphoproteome of skeletal muscle and identified multiple proteins associated in the pathogenesis of EE.
AB - Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Eighty-six differentially altered proteins were identified, of which thirty-seven mitochondrial proteins were differentially expressed, and most of the proteins (37%) were down-regulated in the OXPHOS complex-IV. Also, nine phosphopeptides that correspond to eight mitochondrial proteins were significantly affected in EE patient. These altered proteins recognized are involved in several pathways and molecular functions, predominantly in oxidoreductase activity. This is the first study that has integrated proteome and phosphoproteome of skeletal muscle and identified multiple proteins associated in the pathogenesis of EE.
KW - COX
KW - Ethylmalonic encephalopathy
KW - Mitochondria
KW - Quantitative proteomics
KW - Redox regulation
KW - Skeletal muscle
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U2 - 10.1016/j.mito.2021.02.011
DO - 10.1016/j.mito.2021.02.011
M3 - Article
C2 - 33639274
AN - SCOPUS:85102043290
SN - 1567-7249
VL - 58
SP - 64
EP - 71
JO - Mitochondrion
JF - Mitochondrion
ER -