Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia*

By Huafeng Zhang, M. Bosch-Marce, L. Shimoda, Yee Sun Tan, J. Baek, Jacob B. Wesley, F. Gonzalez, G. Semenza. Journal of Biological Chemistry, 2008

1,599 citations recorded by the source corpus.

Autophagy is a process by which cytoplasmic organelles can be catabolized either to remove defective structures or as a means of providing macromolecules for energy generation under conditions of nutrient starvation. In this study we demonstrate that mitochondrial autophagy is induced by hypoxia, that this process requires the hypoxia-dependent factor-1-dependent expression of BNIP3 and the constitutive expression of Beclin-1 and Atg5, and that in cells subjected to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response which is necessary to prevent increased levels of reactive oxygen species and cell death.

Subfields: Cancer Research, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/721b9f3370352209357fb4dead4d9f5dc0672289

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. G. Semenza
2. Guido Kroemer
3. J. Pouysségur
4. P. Ratcliffe
5. W. Kaelin
6. J. Chiche
7. Cormac T. Taylor
8. Beth Levine

In Epidemiology

1. Beth Levine
2. Guido Kroemer
3. Douglas R. Green
4. V. Deretic
5. L. Galluzzi
6. I. Slaninová
7. G. Semenza
8. Alec C. Kimmelman

In Molecular Biology

1. G. Semenza
2. Guido Kroemer
3. Douglas R. Green
4. Beth Levine
5. L. Galluzzi
6. J. Pouysségur
7. P. Ratcliffe
8. V. Deretic

Citations in the corpus

• Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells (2012, methodology): “(c) HeLa cells were transfected with (Flag)N-Fundc1(1-155)-C(Myc) or (Flag)N-Fundc1(1-139)C(Myc) vectors, respectively.”
• Autophagy: assays and artifacts (2010, background): “Mitophagy is also induced as an adaptive response to hypoxia, allowing the cell to reduce its mitochondrial mass to limit production of damaging reactive oxygen species from the mitochondria at a time when oxygen is not available to accept electrons from the respiratory chain [30,31].”
• Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains (2009, background): “reactive oxygen species production (41).”
• The BCL-2 Family Reunion (2010, background): “For example, hypoxia causes a reduction in mitochondrial mass by autophagy (referred to as mitophagy) that is thought to prevent increased levels of ROS and cell death (Zhang et al., 2008).”
• ADAPTIVE AND MALADAPTIVE CARDIORESPIRATORY RESPONSES TO CONTINUOUS AND INTERMITTENT HYPOXIA MEDIATED BY HYPOXIA-INDUCIBLE FACTORS 1 AND 2 (2012, background): “Whereas the expression of most HIF-1 target genes is negatively regulated by FIH-1, there is a subset of genes (including BNIP3 and PGK1) whose expression is independent of FIH-1, suggesting that transactivation of these genes is dependent only on TAD-N (61).”
• The LIR motif – crucial for selective autophagy (2013, background): “Bnip3 and Nix are both involved in hypoxia-induced mitophagy (Zhang et al., 2008; Bellot et al., 2009).”
• Molecular mechanisms and physiological functions of mitophagy (2021, positive): “BNIP3 is required for efficient turnover of mitochondria under hypoxic conditions (Zhang et al , 2008).”
• Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. (2016, background): “HIF-1 is directly involved in regulating mitochondrial autophagy by inducing expression of the BH3-only proteins BNIP3 andBNIP3L,whichpromotes release of Beclin-1, a major autophagy regulator (Zhang et al., 2008a; Bellot et al., 2009).”