ATP synthase subunit g, mitochondrial and ATP synthase subunit beta, mitochondrial (ATP5L/ATP5B)

Mitochondrial ATP synthase, also known as Complex V, is a multi-subunit molecular motor that catalyzes the synthesis of ATP from ADP and inorganic phosphate, driven by the proton-motive force across the inner mitochondrial membrane [17, 18]. The complex consists of two functional domains: the soluble F1 catalytic core, which includes the ATP5B (beta) subunit, and the membrane-embedded Fo proton channel, which includes the ATP5L (g) subunit [1, 5]. ATP5B is the primary site of ATP synthesis and is a well-characterized target for various inhibitors, including angiostatin and aurovertin B, which are explored for their anti-angiogenic and anti-tumor properties [10]. ATP5L plays a crucial role in the assembly and stability of the Fo domain and the formation of mitochondrial cristae, which are essential for efficient energy production [3, 7]. Beyond its primary role in the mitochondria, an ectopic form of ATP synthase containing ATP5B is found on the surface of certain cells, where it acts as a receptor for angiostatin and participates in HDL endocytosis [10]. Dysregulation or mutation of these subunits is linked to a variety of conditions, including neurodegenerative diseases like Alzheimer's and Parkinson's, where reduced expression or oxidative damage impairs cellular bioenergetics [8, 20, 25]. In cancer, the complex is often overexpressed or localized to the cell surface, making it a target for therapies that aim to suppress tumor growth and angiogenesis [10]. Therapeutic strategies targeting these subunits aim to modulate metabolic pathways, induce apoptosis in cancer cells, or restore mitochondrial function in degenerative states [6, 10, 17]. Drugs like bedaquiline and oligomycin demonstrate the potential of targeting this complex, although systemic toxicity remains a significant challenge due to its essential role in all aerobic cells [17].

Other names

Mitochondrial ATP synthase subunits ATP5L and ATP5BATP synthase subunit beta, mitochondrialATP synthase subunit g, mitochondrialATP5F1BATP5MGComplex V subunitsF1Fo-ATP synthaseATPMBATPSBATP5JG

Inhibition of the catalytic activity of the F1 domain (ATP5B) or the proton channel of the Fo domain (ATP5L) to disrupt ATP synthesis, leading to ATP depletion, activation of the AMPK pathway, and induction of apoptosis or inhibition of angiogenesis.