: 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.
Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy / Di Rita, Anthea; Angelini, Daniela F; Maiorino, Teresa; Caputo, Valerio; Cascella, Raffaella; Kumar, Mukesh; Tiberti, Matteo; Lambrughi, Matteo; Wesch, Nicole; Löhr, Frank; Dötsch, Volker; Carinci, Marianna; D'Acunzo, Pasquale; Chiurchiù, Valerio; Papaleo, Elena; Rogov, Vladimir V; Giardina, Emiliano; Battistini, Luca; Strappazzon, Flavie. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1476-5403. - 28:8(2021), pp. 2499-2516. [10.1038/s41418-021-00766-3]
Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy
Maiorino, Teresa;
2021
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
