Gwangbeom Heo

Abstract Certain human mutations in the mitochondrial aldehyde dehydrogenase 4A1 (ALDH4A1) lead to a severe, paediatric form of epilepsy and developmental abnormalities, yet the precise molecular mechanism leading to the clinical phenotypes remains unexplained. ALDH4A1 metabolizes glutamic-γ-semialdehyde (GSA). Mutations in ALDH4A1, which lead to inactive enzyme variants, cause GSA to accumulate and vitamin B6 inactivation.

1 Introduction Inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, is emerging as a global health concern (Abraham and Cho 2009; Kaplan 2015). Although the exact pathogenic mechanisms remain unclear, intestinal inflammation and epithelial injury are hallmark features of IBD, particularly Crohn's disease and ulcerative colitis (Neurath 2014).

Abstract Fis1-mediated mitochondrial localization of Drp1 and excessive mitochondrial fission occur in human pathologies associated with oxidative stress. However, it is not known how Fis1 detects oxidative stress and what structural changes in Fis1 enable mitochondrial recruitment of Drp1. We find that conformational change involving α1 helix in Fis1 exposes its only cysteine, Cys41.