Autophagy prevents autophagic cell death in <em>Tetrahymena </em>in response to oxidative stress

Si-Wei ZHANG; Jiang-Nan FENG; Yi CAO; Li-Ping MENG; Shu-Lin WANG

Volume 36 Issue 3

May 2015

Turn off MathJax

Article Contents

Article Navigation > Zoological Research > 2015 > 36(3): 167-173

Si-Wei ZHANG, Jiang-Nan FENG, Yi CAO, Li-Ping MENG, Shu-Lin WANG. Autophagy prevents autophagic cell death in Tetrahymena in response to oxidative stress. Zoological Research, 2015, 36(3): 167-173.

Citation:

Si-Wei ZHANG, Jiang-Nan FENG, Yi CAO, Li-Ping MENG, Shu-Lin WANG. Autophagy prevents autophagic cell death in Tetrahymena in response to oxidative stress. Zoological Research, 2015, 36(3): 167-173.

Si-Wei ZHANG, Jiang-Nan FENG, Yi CAO, Li-Ping MENG, Shu-Lin WANG. Autophagy prevents autophagic cell death in Tetrahymena in response to oxidative stress. Zoological Research, 2015, 36(3): 167-173.

Citation:

PDF( 2554 KB)

Autophagy prevents autophagic cell death in Tetrahymena in response to oxidative stress

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China

More Information

Corresponding author: Shu-Lin WANG
Received Date: 2015-03-16
Rev Recd Date: 2015-05-07
Publish Date: 2015-05-08

Abstract

Abstract

Autophagy is a major cellular pathway used to degrade long-lived proteins or organelles that may be damaged due to increased reactive oxygen species (ROS) generated by cellular stress. Autophagy typically enhances cell survival, but it may also act to promote cell death under certain conditions. The mechanism underlying this paradox, however, remains unclear. We showed that Tetrahymena cells exerted increased membrane-bound vacuoles characteristic of autophagy followed by autophagic cell death (referred to as cell death with autophagy) after exposure to hydrogen peroxide. Inhibition of autophagy by chloroquine or 3-methyladenine significantly augmented autophagic cell death induced by hydrogen peroxide. Blockage of the mitochondrial electron transport chain or starvation triggered activation of autophagy followed by cell death by inducing the production of ROS due to the loss of mitochondrial membrane potential. This indicated a regulatory role of mitochondrial ROS in programming autophagy and autophagic cell death in Tetrahymena. Importantly, suppression of autophagy enhanced autophagic cell death in Tetrahymena in response to elevated ROS production from starvation, and this was reversed by antioxidants. Therefore, our results suggest that autophagy was activated upon oxidative stress to prevent the initiation of autophagic cell death in Tetrahymena until the accumulation of ROS passed the point of no return, leading to delayed cell death in Tetrahymena.
- Autophagy,
- Autophagic cell death,
- Lysosome,
- Mitochondria,
- Reactive oxygen species,
- Tetrahymena

FullText(HTML)

References(24)

References

[1]	Amaravadi RK, Yu DN, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. 2007. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. Journal of Clinical Investigation, 117(2): 326-336.
[2]	Baehrecke EH. 2005. Autophagy: Dual roles in life and death?. Nature Reviews Molecular Cell Biology, 6(6): 505-510.
[3]	Bedard K, Krause KH. 2007. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiological Reviews, 87(1): 245-313.
[4]	Ejercito M, Wolfe J. 2003. Caspase-like activity is required for programmed nuclear elimination during conjugation in Tetrahymena. Journal of Eukaryotic Microbiology, 50(6): 427-429.
[5]	Endoh H, Kobayashi T. 2006. Death harmony played by nucleus and mitochondria: nuclear apoptosis during conjugation of Tetrahymena. Autophagy, 2(2): 129-131.
[6]	Kang C, You YJ, Avery L. 2007. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes & Development, 21(17): 2161-2171.
[7]	Klionsky DJ. 2007. Autophagy: from phenomenology to molecular understanding in less than a decade. Nature Reviews Molecular Cell Biology, 8(11): 931-937.
[8]	Kobayashi T, Endoh H. 2003. Caspase-like activity in programmed nuclear death during conjugation of Tetrahymena thermophila. Cell Death and Differentiation, 10(6): 634-640.
[9]	Kroemer G, Levine B. 2008. Autophagic cell death: the story of a misnomer. Nature Reviews Molecular Cell Biology, 9(12): 1004-1010.
[10]	Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G. 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death and Differentiation, 16(1): 3-11.
[11]	Lambeth JD. 2004. NOX enzymes and the biology of reactive oxygen. Nature Reviews Immunology, 4(3): 181-189.
[12]	Levine B, Klionsky DJ. 2004. Development by self-digestion: Molecular mechanisms and biological functions of autophagy. Developmental Cell, 6(4): 463-477.
[13]	Levine B, Kroemer G. 2008. Autophagy in the pathogenesis of disease. Cell, 132(1): 27-42.
[14]	Li WZ, Zhang SW, Numata O, Nozawa Y, Wang SL. 2009. TpMRK regulates cell division of Tetrahymena in response to oxidative stress. Cell Biochemistry and Function, 27(6): 364-369.
[15]	Lu E, Wolfe J. 2001. Lysosomal enzymes in the macronucleus of Tetrahymena during its apoptosis-like degradation. Cell Death and Differentiation, 8(3): 289-297.
[16]	Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, Thompson CB. 2005. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell, 120(2): 237-248.
[17]	Maclean KH, Dorsey FC, Cleveland JL, Kastan MB. 2008. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. Journal of Clinical Investigation, 118(1): 79-88.
[18]	Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. 2007. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews Molecular Cell Biology, 8(9): 741-752.
[19]	Nakashima S, Wang SL, Hisamoto N, Sakai H, Andoh M, Matsumoto K, Nozawa Y. 1999. Molecular cloning and expression of a stress-responsive mitogen-activated protein kinase-related kinase from Tetrahymena cells. Journal of Biological Chemistry, 274(15): 9976-9983.
[20]	Poole B, Ohkuma S. 1981. Effect of weak bases on the intralysosomal ph in mouse peritoneal macrophages. The Journal of Cell Biology, 90(3): 665-669.
[21]	Scherz-Shouval R, Elazar Z. 2007. ROS, mitochondria and the regulation of autophagy. Trends in Cell Biology, 17(9): 422-427.
[22]	Shintani T, Klionsky DJ. 2004. Autophagy in health and disease: A double-edged sword. Science, 306(5698): 990-995.
[23]	Wang SL, Nakashima S, Numata O, Fujiu K, Nozawa Y. 1999. Molecular cloning and cell-cycle-dependent expression of the acetyl-CoA synthetase gene in Tetrahymena cells. Biochemical Journal, 343(2): 479-485.
[24]	Wang S, Nakashima S, Sakai H, Numata O, Fujiu K, Nozawa Y. 1998. Molecular cloning and cell-cycle-dependent expression of a novel NIMA (never-in-mitosis in Aspergillus nidulans)-related protein kinase (TpNrk) in Tetrahymena cells. The Biochemical Journal, 334: 197-203.