Figure 10.

This diagram shows the major pathways and processes regulating mitochondrial bioenergetics and Ca²⁺ homeostasis. It includes mitochondrial substrate transport and oxidation; tricarboxylic acid (TCA) cycle; electron transport chain (ETC), H⁺ pumping, and oxidative phosphorylation (OxPhos); inorganic phosphate carrier (PIC: Pi⁻-H⁺ cotransporter); adenine nucleotide translocase (ANT: ATP-ADP exchanger); and H⁺ leak. It also includes the pathways of mitochondrial Ca²⁺ uptake, release, and buffering regulating mitochondrial Ca²⁺ homeostasis (CU: Ca²⁺ uniporter, NCE: Na⁺/Ca²⁺ exchanger, and NHE: Na⁺/H⁺ exchanger). The diagram also shows the hypothetical regulatory (activation or inhibition) sites of Ca²⁺ on mitochondria OxPhos and ATP synthesis. Ca²⁺ activates mitochondrial dehydrogenase enzymes (PDH: pyruvate dehydrogenase, ICDH: isocitrate dehydrogenase, and OGDH: oxoglutarate dehydrogenase) at low concentrations. However, high concentrations of Ca²⁺ can inhibit mitochondrial complex I and can result in the opening of a mitochondrial permeability transition pore (PTP), leading to mitochondrial dysfunction.