biostudies-literatureJacovetti CUniversity of LausanneSwiss National Science FoundationUniversity of PisaMinistero dell’Istruzione, dell’Università e della RicercaEuropean Commission101955https://www.ebi.ac.uk/biostudies/studies/S-EPMC11112368biostudies-literatureUnknown84<h4>Objective</h4>The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-Leu^TAA) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-Leu^TAA, on mitochondrial metabolism and pancreatic islet functions.<h4>Methods</h4>We used antisense oligonucleotides to reduce mt-tRF-Leu^TAA levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-Leu^TAA inhibition. AdditionaMolecular metabolismThe mitochondrial tRNA-derived fragment, mt-tRF-Leu^TAA, couples mitochondrial metabolism to insulin secretion.PMC11112368PNRR M4C2-I1.3194964310030_219252310030_188447188447310030PE_00000019Jacovetti CWu KBouzakri KMarchetti PSobel JRegazzi RDonnelly CMenoud VCosentino CSuleiman MKayser BGuay CfalseThe mitochondrial tRNA-derived fragment, mt-tRF-Leu^TAA, couples mitochondrial metabolism to insulin secretion.<h4>Objective</h4>The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-Leu^TAA) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-Leu^TAA, on mitochondrial metabolism and pancreatic islet functions.<h4>Methods</h4>We used antisense oligonucleotides to reduce mt-tRF-Leu^TAA levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-Leu^TAA inhibition. Additiona2024-01-01T00:00:00Z2024 Jun2026-07-15T07:57:39.89Z2026-07-01T03:12:11.1ZS-EPMC111123683870402610.1016/j.molmet.2024.101955