Related Experiment Video

Updated: Nov 12, 2025

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
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Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy

Anthea Di Rita1,2, Daniela F Angelini3, Teresa Maiorino4

  • 1Department of Life Sciences, University of Siena, Siena, Italy.

Cell Death and Differentiation
|March 16, 2021
PubMed

Insights

Multiple sclerosis (MS) research reveals a link between the NDP52 gene variant and the disease. This NDP52 variant impacts mitophagy, a cellular cleanup process, potentially influencing inflammation in MS patients.

Area of Science:

  • Cellular Biology
  • Immunology
  • Neuroscience

Background:

  • Multiple sclerosis (MS) is linked to mitochondrial dysfunction, but the role of mitophagy, the process of removing damaged mitochondria, is unclear.
  • PINK1-mediated mitophagy is a key cellular mechanism for mitochondrial quality control.

Purpose of the Study:

  • To investigate the role of PINK1-mediated mitophagy in relapsing-remitting MS.
  • To identify genetic factors and cellular mechanisms influencing mitophagy in MS patients.

Main Methods:

  • Qualitative and quantitative analysis of mitophagy players in peripheral blood mononuclear cells (PBMCs) from MS patients.
  • Genetic association study to identify variants in mitophagy receptor genes.
  • Functional characterization of identified variants, including protein binding assays and assessment of autophagosome formation.
  • Analysis of NDP52 expression in immune cells and its effect on cytokine production.

Main Results:

  • A specific variant (c.491G>A, rs550510, p.G140E) in the NDP52 gene, a mitophagy receptor, was associated with an MS cohort.
  • Residue 140 of human NDP52 is critical for NDP52/LC3C binding, essential for efficient mitophagy.
  • NDP52 is primarily expressed in B cells within PBMCs.
  • Efficient mitophagy mediated by NDP52 limits the production of the pro-inflammatory cytokine TNF-α in response to stimulation.

Conclusions:

  • NDP52 plays a significant role in regulating mitophagy, particularly in B cells.
  • The identified NDP52 variant may contribute to MS pathogenesis by affecting mitophagy efficiency.
  • This study provides the first evidence for a potential role of NDP52 in multiple sclerosis.

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