Mitochondrial thiol-containing proteins

Mitochondrial thiol-containing proteins are a functional class of proteins located within the mitochondria that utilize the redox-active properties of cysteine thiol (-SH) groups for catalysis, structural stability, and signaling (PMID: 22503544). This group encompasses key antioxidant enzymes such as thioredoxin 2 (Trx2), thioredoxin reductase 2 (TrxR2), and peroxiredoxins (Prx3, Prx5), which are vital for neutralizing superoxide and hydrogen peroxide generated during oxidative phosphorylation (PMID: 15822172). Beyond antioxidant defense, these thiols are found in metabolic enzymes like alpha-ketoglutarate dehydrogenase and components of the electron transport chain, where they act as sensors for the mitochondrial redox state (PMID: 28847445). In pathological states such as cancer, mitochondrial thiols are often overexpressed to provide a survival advantage against elevated oxidative stress, whereas in neurodegenerative diseases, their oxidative modification contributes to mitochondrial dysfunction and cell death (PMID: 23603808). Therapeutic strategies often involve the use of electrophilic compounds or metal complexes, such as auranofin, which covalently inhibit these proteins to induce mitochondrial-mediated apoptosis in malignant cells (PMID: 29413440). However, the therapeutic window is often narrow due to the ubiquitous nature of thiol groups in the cytosol and other organelles, necessitating the development of mitochondria-targeted delivery systems (PMID: 25130392).

Other names

Mitochondrial protein thiolsMitochondrial redox-sensitive proteinsMitochondrial thiol proteome

Covalent modification of cysteine thiol groups, inhibition of mitochondrial thioredoxin reductase (TrxR2), and induction of mitochondrial oxidative stress leading to the opening of the mitochondrial permeability transition pore (mPTP) and subsequent apoptosis (PMID: 29413440, PMID: 22503544).