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Molecular and Cellular Biology, December 2001, p. 8483-8489, Vol. 21, No. 24
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.24.8483-8489.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Mitochondrial Respiratory Electron Carriers Are
Involved in Oxidative Stress during Heat Stress in
Saccharomyces cerevisiae
John F.
Davidson and
Robert H.
Schiestl*
Department of Cancer Cell Biology, Harvard
School of Public Health, Boston, Massachusetts 02115
Received 23 August 2001/Accepted 27 September 2001
In the present study we sought to determine the source of
heat-induced oxidative stress. We investigated the involvement of mitochondrial respiratory electron transport in post-diauxic-phase cells under conditions of lethal heat shock. Petite cells were thermosensitive, had increased nuclear mutation frequencies, and experienced elevated levels of oxidation of an intracellular probe following exposure to a temperature of 50°C. Cells with a
deletion in COQ7 leading to a deficiency in coenzyme Q had
a much more severe thermosensitivity phenotype for these oxidative
endpoints following heat stress compared to that of petite cells. In
contrast, deletion of the external NADH dehydrogenases NDE1 and NDE2,
which feed electrons from NADH into the electron transport chain,
abrogated the levels of heat-induced intracellular fluorescence and
nuclear mutation frequency. Mitochondria isolated from
COQ7-deficient cells secreted more than 30 times as much
H2O2 at 42 as at 30°C, while mitochondria
isolated from cells simultaneously deficient in NDE1 and NDE2 secreted
no H2O2. We conclude that heat stress causes
nuclear mutations via oxidative stress originating from the respiratory
electron transport chains of mitochondria.
*
Corresponding author. Mailing address: Deptartment of
Pathology & Environmental Health, UCLA School of Medicine and Public Health, 650 Charles E. Young Dr. South, 71-295 CHS, Los Angeles, CA
90095. Phone: (310) 267-2087. Fax: (310) 267-2578. E-mail: rschiestl{at}mednet.ucla.edu.
Molecular and Cellular Biology, December 2001, p. 8483-8489, Vol. 21, No. 24
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.24.8483-8489.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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