Mitochondrial DNA and mitochondrial proteins (mtDNA and mitochondrial proteins)

Mitochondrial DNA (mtDNA) and mitochondrial proteins constitute the essential genetic and functional components of the mitochondria, the primary site of cellular energy production via oxidative phosphorylation (OXPHOS) [1, 7]. The human mitochondrial genome is a circular, double-stranded DNA molecule that encodes 13 essential subunits of the electron transport chain, along with 22 tRNAs and 2 rRNAs required for their translation [1, 18]. Mitochondrial proteins encompass these 13 mtDNA-encoded subunits as well as over 1,000 nuclear-encoded proteins that are imported into the organelle to regulate metabolism, calcium homeostasis, and the initiation of apoptosis [16, 17]. Dysfunction in mtDNA or mitochondrial proteins is the underlying cause of primary mitochondrial diseases, such as Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and is increasingly implicated in cancer, neurodegeneration, and metabolic syndrome [5, 9, 18]. Therapeutic strategies include the use of mitochondria-targeted antioxidants like MitoQ to reduce oxidative stress, or cardiolipin-stabilizing peptides like elamipretide to restore membrane integrity [1, 4]. Conversely, many drugs exhibit off-target "mitotoxicity," such as nucleoside reverse transcriptase inhibitors (NRTIs) that cause mtDNA depletion by inhibiting DNA polymerase gamma, or certain antibiotics that interfere with mitochondrial protein synthesis [12, 15, 19].

Other names

mtDNAMitochondrial genomeMitochondrial proteomeChondriomeMitochondrial DNA-encoded proteins

Drugs targeting these components act by inhibiting mitochondrial protein synthesis, causing mitochondrial DNA depletion through polymerase gamma inhibition, stabilizing mitochondrial membranes, or scavenging organelle-specific reactive oxygen species [1, 12, 15, 19].