Mitochondrial gene expression requires RNA processing and ribosome assembly to support oxidative phosphorylation. We investigated the hepatocyte-specific roles of MRPP3, the catalytic subunit of mitochondrial RNase P, and PTCD1, a pentatricopeptide repeat protein required for rRNA maturation. Liver-specific deletion of either factor caused early lethality with profound mitochondrial hepatopathy. Mechanistically, MRPP3 loss blocked tRNA processing, while PTCD1 loss destabilized 12S and 16S rRNAs, impairing mitoribosome biogenesis. Both knockouts abolished mitochondrial translation, depleting mtDNA-encoded OXPHOS subunits and collapsing respiratory function. Proteomics revealed depletion of mitoribosomal proteins and compensatory induction of nuclear-encoded stress markers. Transcriptomics showed remodelling of oxidoreductase pathways, while metabolomics uncovered accumulation of amino acids and TCA intermediates, energy depletion, and altered bile acid metabolism, with evidence of compensatory anaplerotic flux. Together, these findings establish MRPP3 and PTCD1 as essential gatekeepers of mitochondrial translation and highlight how their loss drives metabolic collapse and organ-specific pathology.