Autophagy driven by a master regulator of hematopoiesis

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

Research output: Contribution to journalArticle

76 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Kang, Y. A., Sanalkumar, R., O'geen, H., Linnemann, A. K., Chang, C. J., Bouhassira, E. E., Farnham, P. J., Keles, S., & 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