Affiliation:
1. Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115
Abstract
ABSTRACT
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 H
2
O
2
at 42 as at 30°C, while mitochondria isolated from cells simultaneously deficient in NDE1 and NDE2 secreted no H
2
O
2
. We conclude that heat stress causes nuclear mutations via oxidative stress originating from the respiratory electron transport chains of mitochondria.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
185 articles.
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