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Mitophagy protects beta cells from inflammatory damage in diabetes

Vaibhav Sidarala, Gemma L. Pearson, Vishal S. Parekh, Benjamin Thompson, Lisa Christen, Morgan A. Gingerich, Jie Zhu, Tracy Stromer, Jianhua Ren, Emma C. Reck, Biaoxin Chai, John A. Corbett, Thomas Mandrup‐Poulsen, Leslie S. Satin, Scott A. Soleimanpour

bioRxiv (Cold Spring Harbor Laboratory) · 2020 · ▲ 5 citations

Abstract

Abstract Inflammatory damage contributes to β-cell failure in type 1 and 2 diabetes (T1D and T2D). Mitochondria are damaged by inflammatory signaling in β-cells, resulting in impaired bioenergetics and initiation of pro-apoptotic machinery. Hence, the identification of protective responses to inflammation could lead to new therapeutic targets. Here we report that mitophagy serves as a protective response to inflammatory stress in both human and rodent β-cells. Utilizing in vivo mitophagy reporters, we observed that diabetogenic pro-inflammatory cytokines induced mitophagy in response to nitrosative/oxidative mitochondrial damage. Mitophagy-deficient β-cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β-cell death, and hyperglycemia. Overexpression of CLEC16A , a T1D gene and mitophagy regulator whose expression in islets is protective against T1D, ameliorated cytokine-induced human β-cell apoptosis. Thus, mitophagy promotes β-cell survival and prevents diabetes by countering inflammatory injury. Targeting this pathway has the potential to prevent β-cell failure in diabetes and may be beneficial in other inflammatory conditions.

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Provenance

Source
OpenAlex
DOI
10.1101/2020.06.07.138917
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2026-06-26 MST

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APA
Sidarala, V., Pearson, G.L., Parekh, V.S., Thompson, B., Christen, L., Gingerich, M.A., Zhu, J., Stromer, T., Ren, J., Reck, E.C., Chai, B., Corbett, J.A., Mandrup‐Poulsen, T., Satin, L.S., &amp; Soleimanpour, S.A. (2020). Mitophagy protects beta cells from inflammatory damage in diabetes. <em>bioRxiv (Cold Spring Harbor Laboratory)</em>. https://doi.org/10.1101/2020.06.07.138917
Vancouver
Sidarala V, Pearson GL, Parekh VS, Thompson B, Christen L, Gingerich MA, et al. Mitophagy protects beta cells from inflammatory damage in diabetes. bioRxiv (Cold Spring Harbor Laboratory). 2020. doi:10.1101/2020.06.07.138917.
BibTeX
@unpublished{vaibhav2020Mitoph, title = {Mitophagy protects beta cells from inflammatory damage in diabetes}, author = {Vaibhav Sidarala and Gemma L. Pearson and Vishal S. Parekh and Benjamin Thompson and Lisa Christen and Morgan A. Gingerich and Jie Zhu and Tracy Stromer and Jianhua Ren and Emma C. Reck and Biaoxin Chai and John A. Corbett and Thomas Mandrup‐Poulsen and Leslie S. Satin and Scott A. Soleimanpour}, journal = {bioRxiv (Cold Spring Harbor Laboratory)}, year = {2020}, doi = {10.1101/2020.06.07.138917}, }

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