HRI inhibits translation of nuclear encoded mRNAs of mitochondrial proteins and maintains mitochondrial respiration in ID. (A) In addition to inhibiting cytosolic ribosomal protein synthesis, HRI is necessary to inhibit translation of mRNAs encoding mitochondrial ribosomal proteins, oxidative phosphorylation proteins, and matrix proteins during ID. (B) In the absence of HRI, the increased translation of these mRNAs in ID results in increased mitochondrial protein synthesis, which impairs mitochondrial respiration, likely as a result of proteotoxicity. Adapted from Zhang et al with permission.⁴⁶