Two-way communication between the nucleus and mitochondria via a micropeptide in renal fibrosis

Micropeptides are small proteins encoded by short open reading frames mostly located in long noncoding RNAs. Mitoregulin (MOXI) is a nuclear encoded micropeptide initially identified in the inner mitochondrial membrane to regulate fatty acid β-oxidation. In this issue of Kidney International, Li et al. report that MOXI is upregulated in both human fibrotic kidneys and murine models of renal fibrosis. Remarkably, MOXI functions in the nucleus, where it forms a transcriptional complex with N-acetyltransferase 14 and c-Jun to facilitate the expression of fibrotic genes. By working in the nucleus and mitochondria, MOXI may channel the 2-way communication between these organelles, adding a new layer of complexity in the cell biology of renal fibrogenesis. Micropeptides are small proteins encoded by short open reading frames mostly located in long noncoding RNAs. Mitoregulin (MOXI) is a nuclear encoded micropeptide initially identified in the inner mitochondrial membrane to regulate fatty acid β-oxidation. In this issue of Kidney International, Li et al. report that MOXI is upregulated in both human fibrotic kidneys and murine models of renal fibrosis. Remarkably, MOXI functions in the nucleus, where it forms a transcriptional complex with N-acetyltransferase 14 and c-Jun to facilitate the expression of fibrotic genes. By working in the nucleus and mitochondria, MOXI may channel the 2-way communication between these organelles, adding a new layer of complexity in the cell biology of renal fibrogenesis. Mitochondrial micropeptide MOXI promotes fibrotic gene transcription by translocation to the nucleus and bridging N-acetyltransferase 14 with transcription factor c-JunKidney InternationalVol. 103Issue 5PreviewProgressive fibrosis is a hallmark of chronic kidney disease, but we lack effective treatments to halt this destructive process. Micropeptides (peptides of no more than 100 amino acids) encoded by small open reading frames represent a new class of eukaryotic regulators. Here, we describe that the micropeptide regulator of β-oxidation (MOXI) regulates kidney fibrosis. MOXI expression was found to be up-regulated in human fibrotic kidney disease, and this correlated with the degree of fibrosis and loss of kidney function. Full-Text PDF