Atad3a suppresses Pink1-dependent mitophagy to maintain homeostasis of hematopoietic progenitor cells

Guoxiang Jin, Chuan Xu, Xian Zhang, Jie Long, Abdol Hossein Rezaeian, Chunfang Liu, Mark E. Furth, Steven Kridel, Boris Pasche, Xiu Wu Bian, Hui Kuan Lin

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


Although deletion of certain autophagy-related genes has been associated with defects in hematopoiesis, it remains unclear whether hyperactivated mitophagy affects the maintenance and differentiation of hematopoietic stem cells (HSCs) and committed progenitor cells. Here we report that targeted deletion of the gene encoding the AAA+-ATPase Atad3a hyperactivated mitophagy in mouse hematopoietic cells. Affected mice showed reduced survival, severely decreased bone-marrow cellularity, erythroid anemia and B cell lymphopenia. Those phenotypes were associated with skewed differentiation of stem and progenitor cells and an enlarged HSC pool. Mechanistically, Atad3a interacted with the mitochondrial channel components Tom40 and Tim23 and served as a bridging factor to facilitate appropriate transportation and processing of the mitophagy protein Pink1. Loss of Atad3a caused accumulation of Pink1 and activated mitophagy. Notably, deletion of Pink1 in Atad3a-deficient mice significantly 'rescued' the mitophagy defect, which resulted in restoration of the progenitor and HSC pools. Our data indicate that Atad3a suppresses Pink1-dependent mitophagy and thereby serves a key role in hematopoietic homeostasis.

Original languageEnglish (US)
Pages (from-to)29-40
Number of pages12
JournalNature immunology
Issue number1
StatePublished - Jan 1 2018


  • ATPases Associated with Diverse Cellular Activities/genetics
  • Animals
  • Apoptosis/genetics
  • Cell Differentiation/genetics
  • Cell Proliferation/genetics
  • HEK293 Cells
  • Hematopoietic Stem Cells/metabolism
  • Homeostasis
  • Humans
  • Membrane Proteins/genetics
  • Membrane Transport Proteins/genetics
  • Mice, Knockout
  • Mitochondria/genetics
  • Mitochondrial Degradation
  • Mitochondrial Proteins/genetics
  • Protein Kinases/genetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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