| Literature DB >> 33723372 |
Anthea Di Rita1,2, Daniela F Angelini3, Teresa Maiorino4, Valerio Caputo5,6, Raffaella Cascella5,6, Mukesh Kumar7, Matteo Tiberti7, Matteo Lambrughi7, Nicole Wesch8, Frank Löhr8, Volker Dötsch8,9, Marianna Carinci10, Pasquale D'Acunzo11,12, Valerio Chiurchiù3,13, Elena Papaleo7,14, Vladimir V Rogov8,9,15, Emiliano Giardina5,6, Luca Battistini3, Flavie Strappazzon16.
Abstract
The role of mitophagy, a process that allows the removal of damaged mitochondria from cells, remains unknown in multiple sclerosis (MS), a disease that is found associated with dysfunctional mitochondria. Here we have qualitatively and quantitatively studied the main players in PINK1-mediated mitophagy in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting MS. We found the variant c.491G>A (rs550510, p.G140E) of NDP52, one of the major mitophagy receptor genes, associated with a MS cohort. Through the characterization of this variant, we discovered that the residue 140 of human NDP52 is a crucial modulator of NDP52/LC3C binding, promoting the formation of autophagosomes in order to drive efficient mitophagy. In addition, we found that in the PBMC population, NDP52 is mainly expressed in B cells and by ensuring efficient mitophagy, it is able to limit the production of the proinflammatory cytokine TNF-α following cell stimulation. In sum, our results contribute to a better understanding of the role of NDP52 in mitophagy and underline, for the first time, a possible role of NDP52 in MS.Entities:
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Year: 2021 PMID： 33723372 PMCID： PMC8329179 DOI： 10.1038/s41418-021-00766-3
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 12.067