14:00 -14:30 NOX4 effects in Bone Repair: Local and Systemic Perspectives
M.Sc. Mariana de Souza Santos, Ph.D., Laboratory of Molecular Physiology of Bone
Annotation: Bone tissue is influenced by a wide range of local and systemic signals that regulate its homeostasis and regenerative capacity. Obesity can disrupt this balance by promoting bone resorption and increasing fracture risk. One of the changes associated with obesity is the accumulation of adipose tissue within the bone marrow, which contributes to metabolic alterations, including increased NADPH oxidase 4 (NOX4) activity. NOX4 is an enzyme that generates reactive oxygen species (ROS), which act as signaling molecules in both physiological and pathological processes. Emerging evidence suggests that NOX4 may play an important role in regulating bone homeostasis, particularly under metabolically challenging conditions. In this presentation, I will present our recent findings on the role of NOX4 in bone fracture healing animal model under obesogenic conditions from the perspective of the systemic NOX4 deficiency and cell-specific NOX4 inactivation in bone marrow stromal cells. I will also discuss the sex-dependent effects of NOX4 activity during bone healing on bone phenotype and cellular metabolism. Together, these findings provide new insights into the mechanisms underlying bone remodelling and regeneration and may have important implications for the development of therapeutic strategies targeting bone repair and tissue regeneration.
14:30 -15:00 To the molecular mechanism of human cytochrome c oxidase assembly – targeting COX6B1
RNDr. Kristýna Čunátová, Ph.D., Laboratory of Bioenergetics
Annotation: Human cytochrome c oxidase (complex IV, cIV) is the terminal enzyme of the mitochondrial respiratory chain, and defects in its assembly underlie severe mitochondrial diseases. Despite its clinical importance, the assembly pathway remains incompletely understood, particularly its regulation by redox state. This ongoing project investigates COX6B1, a nuclear-encoded cIV subunit whose pathogenic variants cause childhood-onset encephalopathy. Using a COX6B1 knock-out cell line, we have shown that COX6B1 is required not only for late-stage cIV stabilization (as long assumed) but also for early, redox-sensitive assembly steps. Building on these findings, we are now: (I) determining how conserved cysteine motifs of COX6B1 impact cIV assembly; (II) establishing how pathogenic COX6B1 variants affect cIV assembly; (III) characterizing the MT-CO2 maturation intermediate; and (IV) investigating an alternative pathway of cIV assembly directly into respiratory supercomplexes. Together, these findings will advance our understanding of redox-controlled cIV assembly and its relevance to mitochondrial disease pathomechanisms.
Contact at IPHYS: RNDr. Lydie Plecitá, Ph.D.; lydie.plecita@fgu.cas.cz
