Unraveling the functional consequences of a novel germline missense mutation (R38C) in the yeast model of succinate dehydrogenase subunit B: insights into neurodegenerative disorders

Jiatong Zheng; Siru Liu; Dongdong Wang; Linlin Li; Surendra Sarsaiya; Hua Zhou; Heng Cai

doi:10.3389/fnmol.2023.1246842

Unraveling the functional consequences of a novel germline missense mutation (R38C) in the yeast model of succinate dehydrogenase subunit B: insights into neurodegenerative disorders

Front Mol Neurosci. 2023 Sep 28:16:1246842. doi: 10.3389/fnmol.2023.1246842. eCollection 2023.

Authors

Jiatong Zheng¹, Siru Liu¹, Dongdong Wang¹, Linlin Li¹, Surendra Sarsaiya¹, Hua Zhou¹, Heng Cai¹

Affiliation

¹ College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China.

Abstract

This study explores the implications of a novel germline missense mutation (R38C) in the succinate dehydrogenase (SDH) subunit B, which has been linked to neurodegenerative diseases. The mutation was identified from the SDH mutation database and corresponds to the SDH2^R32C allele, mirroring the human SDHB^R38C mutation. By subjecting the mutant yeast model to hydrogen peroxide (H₂O₂) stress, simulating oxidative stress, we observed heightened sensitivity to oxidative conditions. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed significant regulation (p < 0.05) of genes associated with antioxidant systems and energy metabolism. Through gas chromatography-mass spectrometry (GC-MS) analysis, we examined yeast cell metabolites under oxidative stress, uncovering insights into the potential protective role of o-vanillin. This study elucidates the biological mechanisms underlying cellular oxidative stress responses, offering valuable insights into its repercussions. These findings shed light on innovative avenues for addressing neurodegenerative diseases, potentially revolutionizing therapeutic strategies.

Keywords: GC-MS; R32C; Saccharomyces cerevisiae; hydrogen peroxide stress; qRT-PCR; succinate dehydrogenase.

Grants and funding

This study was supported by the 973 Program of China (No. 2013CB733904), and Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. KYCX18_1116).