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BibTex format

@article{Sarwat:2026:10.64898/2026.01.12.697845,
author = {Sarwat, S and Alen, R and Wu, Z and Zhang, C and Paszek, M and Yang, M and Ostinelli, G and Mihalovits, A and Baker, B and Wai, T and Rutter, GA and Rodriguez, TA and Martinez-Sanchez, A},
doi = {10.64898/2026.01.12.697845},
journal = {bioRxiv},
title = {MTFP1 preserves β-cell cristae structure and bioenergetics to ensure insulin release and glucose homeostasis.},
url = {http://dx.doi.org/10.64898/2026.01.12.697845},
year = {2026}
}
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TY  - JOUR
AB  - Pancreatic β-cells are uniquely dependent on mitochondrial metabolism to couple glucose sensing to insulin secretion, a process impaired in diabetes. Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane protein that plays pleiotropic, tissue-specific roles in mitochondrial function and dynamics. Our previous work has identified Mtfp1 mRNA as a target for miR-125b, a microRNA that negatively regulates insulin secretion from β-cells. Nevertheless, the function of MTFP1 in these cells remained unexplored. Here, we show that MTFP1 is essential for normal glucose-stimulated insulin secretion (GSIS) in mouse and human cell lines and islets, and that mice with β-cell-specific elimination of MTFP1 develop glucose intolerance. Whereas β-cell survival and mitochondrial content were unaffected, oxidative phosphorylation and ATP production were sharply lowered. These changes were accompanied by disruption of mitochondrial cristae structure and a reduced contact surface with the endoplasmic reticulum, providing a mechanistic basis for defective stimulus-secretion coupling. Conversely, MTFP1 overexpression in mouse and human islets sufficed to improve mitochondrial respiration and GSIS. Finally, MTFP1 downregulation blocked the positive effects of miR-125b elimination in GSIS and mitochondrial respiration, unveiling MTFP1 as a downstream effector of miR-125b. Together, our findings identify MTFP1 as a critical regulator of β-cell mitochondrial architecture and function, necessary for efficient insulin secretion and glucose homeostasis, and a potential therapeutic target to enhance β-cell bioenergetic resilience in diabetes.
AU  - Sarwat,S
AU  - Alen,R
AU  - Wu,Z
AU  - Zhang,C
AU  - Paszek,M
AU  - Yang,M
AU  - Ostinelli,G
AU  - Mihalovits,A
AU  - Baker,B
AU  - Wai,T
AU  - Rutter,GA
AU  - Rodriguez,TA
AU  - Martinez-Sanchez,A
DO  - 10.64898/2026.01.12.697845
PY  - 2026///
TI  - MTFP1 preserves β-cell cristae structure and bioenergetics to ensure insulin release and glucose homeostasis.
T2  - bioRxiv
UR  - http://dx.doi.org/10.64898/2026.01.12.697845
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41648185
ER  -
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