Dramatic changes in mitochondrial substrate use at critically high temperatures: a comparative study using Drosophila

Author:

Jørgensen Lisa BjerregaardORCID,Overgaard JohannesORCID,Hunter-Manseau FlorenceORCID,Pichaud NicolasORCID

Abstract

AbstractEctotherm thermal tolerance is critical to species distribution, but at present the physiological underpinnings of heat tolerance remain poorly understood. Mitochondrial function is perturbed at critically high temperatures in some ectotherms, including insects, suggesting that heat tolerance of these animals is linked to failure of oxidative phosphorylation (OXPHOS) and/or ATP production. To test this hypothesis we measured mitochondrial oxygen consumption rates in six Drosophila species with different heat tolerance using high-resolution respirometry. Using a substrate-uncoupler-inhibitor titration protocol we examined specific steps of the electron transport system to study how temperatures below, bracketing and above organismal heat limits affected mitochondrial function and substrate oxidation. At benign temperatures (19 and 30°C), complex I-supported respiration (CI-OXPHOS) was the most significant contributor to maximal OXPHOS. At higher temperatures (34, 38, 42 and 46°C), CI-OXPHOS decreased considerably, ultimately to very low levels at 42 and 46°C. The enzymatic catalytic capacity of complex I was intact across all temperatures and accordingly the decreased CI-OXPHOS is unlikely to be caused directly by hyperthermic denaturation/inactivation of complex I. Despite the reduction in CI-OXPHOS, maximal OXPHOS capacities were maintained in all species, through oxidation of alternative substrates; proline, succinate and, particularly, glycerol-3-phosphate, suggesting important mitochondrial flexibility at temperatures exceeding the organismal heat limit. Interestingly, this compensatory oxidation of alternative substrates occurred at temperatures that tended to correlate with species heat tolerance, such that heat-tolerant species could defend “normal” mitochondrial function at higher temperatures than sensitive species. Future studies should investigate why CI-OXPHOS is perturbed and how this potentially affects ATP production rates.

Publisher

Cold Spring Harbor Laboratory

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