Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

Figure 1

Succession of events leading to sepsis-induced mitochondrial dysfunction. (1) Increased activity of inducible NO-synthase. (2) Increased mitochondrial superoxide anion generation. (3) Production of peroxynitrite. (4) Nitrosylation of respiratory chain complexes. (5) Decreased membrane potential. (6) Opening of mitochondrial transition pore. Greek numbers refer to mitochondrial complexes. iNOS: inducible nitric oxide synthase; NO: nitric oxide; : superoxide anion; ONOO⁻: peroxynitrite; O₂: oxygen; ADP: adenosine diphosphate; ATP: adenosine triphosphate; H⁺: proton; FADH₂: reduced flavin-adenine dinucleotide; FAD⁺: oxidized flavin-adenine dinucleotide; NADH: reduced nicotinamide adenine dinucleotide; NAD⁺: oxidized nicotinamide adenine dinucleotide; Ca⁺⁺: ionized calcium; mPTP: mitochondrial permeability transition pore.