Clinical Bioenergetics

The impairment of biological tissue caused by ischemia is a key area of research in both natural sciences and medical research. The utilization of oxygen in the process of tissue respiration is closely linked to mitochondrial function, i.e., the directed transfer of electrons between the enzyme complexes of the respiratory chain. The Cytochrome c oxidase, complex IV of the ETC, represents the so-called “rate-limiting step.” Kadenbach’s theory has described different activity states of this enzyme, which are crucial for the production of oxygen radicals. This mechanism is an important part of understanding ischemic damage to the heart.

Objective: Resistance exercise can induce muscle damage that impairs sports performance and cellular repair. Myokines, particularly mitochondrial myokines, play an important role in regulating energy metabolism and muscle recovery. The ACTN3 R577X polymorphism, which alters the expression of α-actinin-3 in muscle fibers, may influence myokine responses by modulating exercise adaptation and recovery. Methods: Seventy-five amateur runners (30–55 years) from the São Paulo International Marathon were evaluated. Plasma levels of mitochondrial myokines (BDNF, FGF-21, FSTL, IL-6, apelin, IL-15, musclin, and myostatin) were measured before and after the race and correlated with ACTN3 R577X genotypes. Results: In this study, the genotypic frequencies of the ACTN3 R577X polymorphism were 36% (RR), 39% (RX), and 14% (XX). Plasma concentrations of BDNF, FSTL, FGF-21, and IL-6 increased immediately after running across all genotypes, with no significant differences observed between genotypes. In contrast, plasma levels of myostatin, musclin, IL-15, and apelin decreased during the recovery period only among runners carrying the R allele. Conclusions: Mitochondrial myokine responses to resistance exercise were not substantially different among genotypes of the ACTN3 R577X polymorphism. However, myokines associated with protein breakdown and bioenergetic adaptation were reduced during the recovery period in runners carrying the R allele, which may impact muscle repair and bioenergetic adaptation.

Myeloid malignancies exhibit profound metabolic dependence on mitochondrial oxidative phosphorylation (OXPHOS) for survival and proliferation. Antileukemic therapies such as Venetoclax combined with Azacitidine or cytarabine induce rapid mitochondrial collapse, disrupting electron transport, NADH oxidation, and ATP synthesis, followed by a selective rebound of fatty-acid oxidation (FAO) and redox-buffering programs that sustain minimal residual disease. This review integrates current mechanistic and clinical insights into therapy-induced mitochondrial suppression, delineates the regulatory circuitry that enables metabolic recovery, and frames these events as a reversible model of clinical energy deficiency. By linking mitochondrial stress signaling, lipid oxidation, and adaptive redox metabolism, we outline how bioenergetic reprogramming drives therapeutic resistance and propose interventions that target this adaptive axis in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and related myeloid neoplasms.