Autophagy driven by a master regulator of hematopoiesis

Yoon A. Kang, Rajendran Sanalkumar, Henriette O'geen, Amelia Linnemann, Chan Jung Chang, Eric E. Bouhassira, Peggy J. Farnham, Sunduz Keles, Emery H. Bresnick

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery functions in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell-type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis, GATA-1, directly activates transcription of genes encoding the essential autophagy component microtubule-associated protein 1 light chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, and GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell-type-specific autophagy.

Original languageEnglish (US)
Pages (from-to)226-239
Number of pages14
JournalMolecular and Cellular Biology
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Autophagy
Hematopoiesis
Light
Forkhead Transcription Factors
Microtubule-Associated Proteins
Erythropoiesis
Essential Genes
Lysosomes
Organelles
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Kang, Y. A., Sanalkumar, R., O'geen, H., Linnemann, A., Chang, C. J., Bouhassira, E. E., ... Bresnick, E. H. (2012). Autophagy driven by a master regulator of hematopoiesis. Molecular and Cellular Biology, 32(1), 226-239. https://doi.org/10.1128/MCB.06166-11

Autophagy driven by a master regulator of hematopoiesis. / Kang, Yoon A.; Sanalkumar, Rajendran; O'geen, Henriette; Linnemann, Amelia; Chang, Chan Jung; Bouhassira, Eric E.; Farnham, Peggy J.; Keles, Sunduz; Bresnick, Emery H.

In: Molecular and Cellular Biology, Vol. 32, No. 1, 01.01.2012, p. 226-239.

Research output: Contribution to journalArticle

Kang, YA, Sanalkumar, R, O'geen, H, Linnemann, A, Chang, CJ, Bouhassira, EE, Farnham, PJ, Keles, S & Bresnick, EH 2012, 'Autophagy driven by a master regulator of hematopoiesis', Molecular and Cellular Biology, vol. 32, no. 1, pp. 226-239. https://doi.org/10.1128/MCB.06166-11
Kang YA, Sanalkumar R, O'geen H, Linnemann A, Chang CJ, Bouhassira EE et al. Autophagy driven by a master regulator of hematopoiesis. Molecular and Cellular Biology. 2012 Jan 1;32(1):226-239. https://doi.org/10.1128/MCB.06166-11
Kang, Yoon A. ; Sanalkumar, Rajendran ; O'geen, Henriette ; Linnemann, Amelia ; Chang, Chan Jung ; Bouhassira, Eric E. ; Farnham, Peggy J. ; Keles, Sunduz ; Bresnick, Emery H. / Autophagy driven by a master regulator of hematopoiesis. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 1. pp. 226-239.
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