Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy

Anthea Di Rita, Daniela F. Angelini, Teresa Maiorino, Valerio Caputo, Raffaella Cascella, Mukesh Kumar, Matteo Tiberti, Matteo Lambrughi, Nicole Wesch, Frank Löhr, Volker Dötsch, Marianna Carinci, Pasquale D’Acunzo, Valerio Chiurchiù, Elena Papaleo, Vladimir V. Rogov, Emiliano Giardina, Luca Battistini, Flavie Strappazzon

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalCell Death and Differentiation
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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