Cellular thiols and mitochondrial membranes

Cellular thiols and mitochondrial membranes refers to a multi-component biological system essential for redox regulation and cell survival. Cellular thiols, including the tripeptide glutathione and various protein-bound sulfhydryl groups, serve as the primary defense against oxidative damage and are critical for maintaining the structural integrity of many enzymes (Miller et al., 2002, Blood). Mitochondrial membranes are the site of oxidative phosphorylation and play a decisive role in apoptosis by regulating the release of pro-apoptotic factors into the cytosol (Green & Kroemer, 2004, Science). Drugs such as arsenic trioxide and auranofin target this system by reacting with thiol groups and causing a loss of mitochondrial membrane potential, which effectively induces cell death in susceptible cancer cells (Chen et al., 1997, Blood; Rigobello et al., 2002, British Journal of Pharmacology). This system is particularly relevant in the context of cancer therapy, where the induction of oxidative stress is used to selectively kill malignant cells. However, the lack of specificity can lead to significant safety concerns, including systemic toxicity and damage to healthy tissues. Because this term encompasses a wide array of molecules and organelle structures, it is considered a physiological mechanism or a broad therapeutic target area rather than a single, discrete molecular entity.

Other names

Intracellular thiolsMitochondrial membrane systemRedox-active thiolsMitochondrial permeability transition pore (MPTP) complex

Induction of oxidative stress through the depletion of intracellular thiols and the disruption of mitochondrial membrane potential, leading to the activation of the intrinsic apoptotic pathway.