This study investigates the coordinated gene expression processes in human cells to produce oxidative phosphorylation (OXPHOS) complexes, which are essential for cellular respiration. The researchers compared the life cycles of nuclear and mitochondrial messenger RNAs (mt-mRNAs) in detail, including transcript production, processing, ribosome association, and degradation. They found significant differences in the kinetic rates of these processes between the two compartments. Specifically, mt-mRNAs were produced 1100-fold higher, degraded 7-fold faster, and accumulated to 160-fold higher levels compared to nuclear mRNAs. The study identified critical regulatory points, such as the role of LRPPRC and FASTKD5 in mt-mRNA stability and processing. The results suggest that the balance between nuclear and mitochondrial gene expression is maintained through slower mitochondrial translation rates, which are orders of magnitude slower than cytosolic translation rates. This kinetic framework provides insights into the complex regulation of OXPHOS subunit biogenesis and highlights the importance of mitonuclear co-regulation in maintaining cellular function.This study investigates the coordinated gene expression processes in human cells to produce oxidative phosphorylation (OXPHOS) complexes, which are essential for cellular respiration. The researchers compared the life cycles of nuclear and mitochondrial messenger RNAs (mt-mRNAs) in detail, including transcript production, processing, ribosome association, and degradation. They found significant differences in the kinetic rates of these processes between the two compartments. Specifically, mt-mRNAs were produced 1100-fold higher, degraded 7-fold faster, and accumulated to 160-fold higher levels compared to nuclear mRNAs. The study identified critical regulatory points, such as the role of LRPPRC and FASTKD5 in mt-mRNA stability and processing. The results suggest that the balance between nuclear and mitochondrial gene expression is maintained through slower mitochondrial translation rates, which are orders of magnitude slower than cytosolic translation rates. This kinetic framework provides insights into the complex regulation of OXPHOS subunit biogenesis and highlights the importance of mitonuclear co-regulation in maintaining cellular function.