Autophagy-dependent and -independent mechanisms of mitochondrial clearance during reticulocyte maturation

Ji Zhang, Paul A. Ney

Research output: Contribution to journalShort survey

19 Citations (Scopus)

Abstract

Erythrocyte formation involves the elimination of mitochondria at the reticulocyte stage of development. Nix-/- reticulocytes fail to eliminate their mitochondria at this step due to a defect in the targeting of mitochondria to autophagosomes. To determine the role of autophagy in this process, we generated Atg7-/- transplant mice. Atg7-/- reticulocytes exhibit a partial defect in mitochondrial clearance, demonstrating that there are both autophagy-dependent and -independent mechanisms of mitochondrial clearance. We used Atg7-/- autophagy-defective reticulocytes to study temporal events in mitochondrial clearance. Mitochondrial depolarization precedes elimination, but in Atg7-/- reticulocytes the depolarization event is markedly delayed. Since Atg7 regulates autophagosome formation, we infer that mitochondrial depolarization occurs downstream of autophagosome formation in reticulocytes. We propose that there are two mechanisms of mitochondrial clearance: one that is triggered by mitochondrial depolarization, and a second NIX-dependent mechanism, which is not. The NIX-dependent mechanism remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)1064-1065
Number of pages2
JournalAutophagy
Volume5
Issue number7
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

Fingerprint

Reticulocytes
Autophagy
Mitochondria
Erythrocytes
Transplants
Autophagosomes

Keywords

  • Atg7
  • Autophagy
  • Mitochondria
  • Mitochondrial clearance
  • Mitochondrial depolarization
  • Mitophagy
  • NIX
  • Reticulocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Autophagy-dependent and -independent mechanisms of mitochondrial clearance during reticulocyte maturation. / Zhang, Ji; Ney, Paul A.

In: Autophagy, Vol. 5, No. 7, 01.10.2009, p. 1064-1065.

Research output: Contribution to journalShort survey

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N2 - Erythrocyte formation involves the elimination of mitochondria at the reticulocyte stage of development. Nix-/- reticulocytes fail to eliminate their mitochondria at this step due to a defect in the targeting of mitochondria to autophagosomes. To determine the role of autophagy in this process, we generated Atg7-/- transplant mice. Atg7-/- reticulocytes exhibit a partial defect in mitochondrial clearance, demonstrating that there are both autophagy-dependent and -independent mechanisms of mitochondrial clearance. We used Atg7-/- autophagy-defective reticulocytes to study temporal events in mitochondrial clearance. Mitochondrial depolarization precedes elimination, but in Atg7-/- reticulocytes the depolarization event is markedly delayed. Since Atg7 regulates autophagosome formation, we infer that mitochondrial depolarization occurs downstream of autophagosome formation in reticulocytes. We propose that there are two mechanisms of mitochondrial clearance: one that is triggered by mitochondrial depolarization, and a second NIX-dependent mechanism, which is not. The NIX-dependent mechanism remains to be elucidated.

AB - Erythrocyte formation involves the elimination of mitochondria at the reticulocyte stage of development. Nix-/- reticulocytes fail to eliminate their mitochondria at this step due to a defect in the targeting of mitochondria to autophagosomes. To determine the role of autophagy in this process, we generated Atg7-/- transplant mice. Atg7-/- reticulocytes exhibit a partial defect in mitochondrial clearance, demonstrating that there are both autophagy-dependent and -independent mechanisms of mitochondrial clearance. We used Atg7-/- autophagy-defective reticulocytes to study temporal events in mitochondrial clearance. Mitochondrial depolarization precedes elimination, but in Atg7-/- reticulocytes the depolarization event is markedly delayed. Since Atg7 regulates autophagosome formation, we infer that mitochondrial depolarization occurs downstream of autophagosome formation in reticulocytes. We propose that there are two mechanisms of mitochondrial clearance: one that is triggered by mitochondrial depolarization, and a second NIX-dependent mechanism, which is not. The NIX-dependent mechanism remains to be elucidated.

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