Respiratory Substrates Regulate S‑Nitrosylation of Mitochondrial Proteins through a Thiol-Dependent Pathway

ABSTRACT: S-Nitrosylation is a reversible post-translational modification on cysteinyl thiols that can modulate the function of redox-sensitive proteins. The S-nitrosylation of mitochondrial proteins has been shown to regulate various mitochondrial activities involved in energy-transducing systems and mitochondrion-driven apoptosis. In isolated rat brain mitochondria, we demonstrate that mitochondrial protein S-nitrosylation is regulated by respiratory substrates (glutamate/malate) through a thiol-dependent pathway. Mitochondrial proteins become susceptible to S-nitro-soglutathione (GSNO)-induced S-nitrosylation in mitochondria with an oxidized environmen