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The role of nuclear-encoded subunits of cytochrome c oxidase in mitochondrial metabolism
Čunátová, Kristýna ; Pecina, Petr (advisor) ; Gahura, Ondřej (referee) ; Ugalde, Cristina (referee)
Mitochondria, 'the powerhouses of the cell', house the integral metabolism pathway of oxidative phosphorylation to produce the majority of cellular energy. Mammalian cytochrome c oxidase, also called complex IV (cIV), is indispensable for the overall oxidative phosphorylation function as the terminal oxidase, and for its regulation to sustain energetic needs. Since cIV is a multimeric enzyme composed of subunits encoded by nuclear and mitochondrial genomes, its biogenesis is a complicated process, which needs to be coordinated to complete a fully functional complex. Further, the setup of individual nuclear-encoded subunits isoforms of cIV may fine-tune cIV function based on the tissue or the environment context. Despite the physiological and pathological relevance of cIV composition, biogenesis, and the secondary deficiencies triggered by cIV defects, nuclear-encoded subunits' function remains poorly understood. At first, mammalian COX4 subunit isoforms with tissue- and oxygen-dependent expression were studied in the HEK293 cellular model with an exclusive expression of COX4I1 or COX4I2 isoform. Remarkably, the COX4I2 isozyme showed lower affinity to oxygen, which may imply regulation of cIV activity under hypoxia, and is of physiological relevance for the oxygen-sensing mechanism. Further,...
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