Do Mitochondria Limit Hot Fish Hearts? Understanding the Role of Mitochondrial Function with Heat Stress in Notolabrus celidotus

Abstract

Hearts are the first organs to fail in animals exposed to heat stress. Predictions of climate change mediated increases in ocean temperatures suggest that the ectothermic heart may place tight constraints on the diversity and distribution of marine species with cardiovascular systems. For many such species, their upper temperature limits (Tmax) and respective heart failure (HF) temperature (THF) are only a few degrees from current environmental temperatures. While the ectothermic cardiovascular system acts as an “ecological thermometer,” the exact mechanism that mediates HF remains unresolved. We propose that heat-stressed cardiac mitochondria drive HF. Using a common New Zealand fish, Notolabrus celidotus, we determined the THF (27.5°C). Haemoglobin oxygen saturation appeared to be unaltered in the blood surrounding and within heat stressed hearts. Using high resolution respirometry coupled to fluorimeters, we explored temperature-mediated changes in respiration, ROS and ATP production, and overlaid these changes with THF. Even at saturating oxygen levels several mitochondrial components were compromised before THF. Importantly, the capacity to efficiently produce ATP in the heart is limited at 25°C, and this is prior to the acute THF for N. celidotus. Membrane leakiness increased significantly at 25°C, as did cytochrome c release and permeability to NADH. Maximal flux rates and the capacity for the electron transport system to uncouple were also altered at 25°C. These data indicate that mitochondrial membrane integrity is lost, depressing ATP synthesis capacity and promoting cytochrome c release, prior to THF. Mitochondria can mediate HF in heat stressed hearts in fish and play a significant role in thermal stress tolerance, and perhaps limit species distributions by contributing to HF.

Thermal acclimation and subspecies-specific effects on heart and brain mitochondrial performance in a eurythermal teleost (Fundulus heteroclitus)

“…Similarly, for 15°C acclimated fish (CT max =∼37°C), we observed level or declining oxygen consumption between T assay =33 and 37°C. Although it is difficult to make causal connections between acute temperature effects on mitochondrial performance and declines in tissue or organism function (though see Iftikar and Hickey, 2013), our results are nonetheless suggestive of a role of declining mitochondrial function in the setting of upper thermal tolerance limits in warm-acclimated fish.…”

“…These constraints are due, at least in part, to temperature effects on biochemical reaction rates and, by extrapolation, aerobic metabolism (Hochachka and Somero, 2002;Schulte, 2015;Guderley and St-Pierre, 2002;Pörtner, 2001;Pörtner and Farrell, 2008). Declines in aerobic performance at thermal extremes are thought to occur because of an inability to deliver O 2 to systemic tissues, possibly owing to effects on cardiac function (Pörtner, 2001;Somero, 2010;Iftikar and Hickey, 2013). Alternatively, temperature-induced declines in neural function are suggested to constrain thermal performance limits (Somero and DeVries, 1967;Ern et al, 2015;Cossins, 1977;Jastroch et al, 2007;Miller and Stillman, 2012).…”

“…For example, the capacity for heart mitochondrial ATP synthesis declines at temperatures preceding heart failure in Notolabrus celidotus (Iftikar and Hickey, 2013). However, no studies have examined the possibility of mitochondrial failure being associated with temperature-induced declines in neural performance.…”

Dynamic changes in cardiac mitochondrial metabolism during warm acclimation in rainbow trout

“…This P/L reduction coincided with an increased mitochondrial oxygen consumption after the addition of exogenous cytochrome c. Cytochrome c is a peripheral protein of the mitochondrial inner membrane that is only loosely bound and is essential for the transport of electrons between complex III and complex IV. If the outer membrane of mitochondria is damaged, the endogenous cytochrome c can be released and the addition of exogenous cytochrome c will increase the mitochondrial oxygen consumption (Hand and Menze, 2008;Kuznetsov et al, 2008;Iftikar and Hickey, 2013). The increased cytochrome c effect observed between day 0 and day 1 with acute warming therefore suggests an impaired mitochondrial functional capacity.…”

“…reversible phenotypic plasticity) may allow some species to fully or partially mitigate the direct thermodynamic effects on oxygen consumption rate and key cardiovascular variables such as heart rate (Ekström et al, 2016a;Sandblom et al, 2016). Such thermal responses at the whole-animal level can be linked to the need to redirect fuel reserves to power the metabolic pathways leading to the aerobic production of ATP by mitochondria (Iftikar and Hickey, 2013). Indeed, mitochondrial oxygen consumption and citrate synthase (CS) activity (a key enzyme of the tricarboxylic acid cycle and a proxy for aerobic metabolism) have been shown to follow a similar pattern as the whole-animal metabolic rate during both acute and chronic temperature changes, although on a different scale (White et al, 2012).…”