Mitochondrial DNA and membranes (mtDNA and mitochondrial membranes)

Mitochondrial DNA (mtDNA) and mitochondrial membranes are essential structural and functional components of the mitochondria, responsible for cellular energy production and metabolic regulation [1]. The mtDNA is a circular, double-stranded molecule that encodes 13 essential proteins of the oxidative phosphorylation (OXPHOS) system, while the inner and outer mitochondrial membranes provide the physical framework for the electron transport chain and regulate the transport of ions and metabolites [2]. Dysfunctions in these components are central to the pathogenesis of mitochondrial diseases, such as MELAS and LHON, and contribute to the progression of neurodegenerative disorders and cancer [5]. Therapeutic strategies include the use of small molecules like elamipretide, which binds to cardiolipin in the inner membrane to stabilize its structure and improve bioenergetics [3]. Conversely, certain drugs like doxorubicin or nucleoside reverse transcriptase inhibitors (NRTIs) can cause unintended mitotoxicity by damaging mtDNA or inhibiting its replication, leading to adverse effects like lactic acidosis [4].

Other names

Mitochondrial genome and lipid bilayersmtDNA and mitochondrial envelopeMitochondrial matrix DNA and inner/outer membranes

Drugs targeting these components act by intercalating into or forming adducts with mtDNA to inhibit replication and transcription, or by binding to specific membrane lipids like cardiolipin to stabilize the inner membrane and optimize the electron transport chain [3, 4].