Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-Sensing, Metabolism, and Dynamics.

Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-Sensing, Metabolism, and Dynamics. Compr Physiol. 2020 Mar 12;10(2):713-765 Authors: Dasgupta A, Wu D, Tian L, Xiong PY, Dunham-Snary KJ, Chen KH, Alizadeh E, Motamed M, Potus F, Hindmarch CCT, Archer SL Abstract In lung vascular cells, mitochondria serve a canonical metabolic role, governing energy homeostasis. In addition, mitochondria exist in dynamic networks, which serve noncanonical functions, including regulation of redox signaling, cell cycle, apoptosis, and mitochondrial quality control. Mitochondria in pulmonary artery smooth muscle cells (PASMC) are oxygen sensors and initiate hypoxic pulmonary vasoconstriction. Acquired dysfunction of mitochondrial metabolism and dynamics contribute to a cancer-like phenotype in pulmonary arterial hypertension (PAH). Acquired mitochondrial abnormalities, such as increased pyruvate dehydrogenase kinase (PDK) and pyruvate kinase muscle isoform 2 (PKM2) expression, which increase uncoupled glycolysis (the Warburg phenomenon), are implicated in PAH. Warburg metabolism sustains energy homeostasis by the inhibition of oxidative metabolism that reduces mitochondrial apoptosis, allowing unchecked cell accumulation. Warburg metabolism is initiated by the induction of a pseudohypoxic state, in which DNA methyltransferase (DNMT)-mediated changes in redox signaling cause normoxic activation of HIF-1α and increase PDK expression....
Source: Comprehensive Physiology - Category: Physiology Tags: Compr Physiol Source Type: research