Acidosis Maintains the Function of Brain Mitochondria in Hypoxia-Tolerant Triplefin Fish: A Strategy to Survive Acute Hypoxic Exposure?

Abstract

The vertebrate brain is generally very sensitive to acidosis, so a hypoxia-induced decrease in pH is likely to have an effect on brain mitochondria (mt). Mitochondrial respiration (JO2) is required to generate an electrical gradient (ΔΨm) and a pH gradient to power ATP synthesis, yet the impact of pH modulation on brain mt function remains largely unexplored. As intertidal fishes within rock pools routinely experience hypoxia and reoxygenation, they would most likely experience changes in cellular pH. We hence compared four New Zealand triplefin fish species ranging from intertidal hypoxia-tolerant species (HTS) to subtidal hypoxia-sensitive species (HSS). We predicted that HTS would tolerate acidosis better than HSS in terms of sustaining mt structure and function. Using respirometers coupled to fluorimeters and pH electrodes, we titrated lactic-acid to decrease the pH of the media, and simultaneously recorded JO2, ΔΨm, and H+ buffering capacities within permeabilized brain and swelling of mt isolated from non-permeabilized brains. We then measured ATP synthesis rates in the most HTS (Bellapiscus medius) and the HSS (Forsterygion varium) at pH 7.25 and 6.65. Mitochondria from HTS brain did have greater H+ buffering capacities than HSS mt (∼10 mU pH.mgprotein-1). HTS mt swelled by 40% when exposed to a decrease of 1.5 pH units, and JO2 was depressed by up to 15% in HTS. However, HTS were able to maintain ΔΨm near -120 mV. Estimates of work, in terms of charges moved across the mt inner-membrane, suggested that with acidosis, HTS mt may in part harness extra-mt H+ to maintain ΔΨm, and could therefore support ATP production. This was confirmed with elevated ATP synthesis rates and enhanced P:O ratios at pH 6.65 relative to pH 7.25. In contrast, mt volumes and ΔΨm decreased downward pH 6.9 in HSS mt and paradoxically, JO2 increased (∼25%) but ATP synthesis and P:O ratios were depressed at pH 6.65. This indicates a loss of coupling in the HSS with acidosis. Overall, the mt of these intertidal fish have adaptations that enhance ATP synthesis efficiency under acidic conditions such as those that occur in hypoxic or reoxygenated brain.

The Role of Reversible Protein Phosphorylation in Regulation of the Mitochondrial Electron Transport System During Hypoxia and Reoxygenation Stress in Marine Bivalves

“…Regulation of mitochondrial metabolism is essential for tolerance to H/R stress that requires rapid transitions between inactive and active metabolic states and mitigation of the undesirable side reactions generating ROS. Consistent with this notion, mitochondrial reorganization including modulation of the OXPHOS pathways was shown to play a key role in responses to H/R stress in different groups including mammals, fish, insects, and mollusks (Kim et al, 2011;Ali et al, 2012;Pamenter, 2014;Martos-Sitcha et al, 2017;Devaux et al, 2019;Gerber et al, 2019;Napolitano et al, 2019;Sokolova et al, 2019). In hypoxia-sensitive organisms such as terrestrial mammals, H/R stress commonly leads to suppression of OXPHOS and ETS activity, elevated ROS production, mitochondrial Ca 2+ overload and collapse of the mitochondrial membrane potential, culminating in cell death (Kalogeris et al, 2012;Ham and Raju, 2016;Andrienko et al, 2017).…”

Interspecific variation in hypoxia tolerance and hypoxia acclimation responses in killifish from the family Fundulidae

“…Variation in the capacity and availability of fuel reserves to support anaerobic metabolism could also have been important; in sculpins, for example, interspecific variation in t LOE is associated with variation in glycogen reserves and lactate dehydrogenase activity in the brain (Mandic et al, 2013;Speers-Roesch et al, 2013). The detrimental effects of metabolic acidosis may have differed between species as well; among triplefin fish, for example, hypoxia-tolerant species are less susceptible to acidosis-induced mitochondrial dysfunction (Devaux et al, 2019).…”

Effects of intermittent hypoxia-hyperoxia on mobility and perceived health in geriatric patients performing a multimodal training intervention: a randomized controlled trial

“…Exercise combined with hypoxic training also improved cognitive function of older individuals [14], and the addition of hyperoxic intervals might have accelerated clearance of metabolites negatively impacting on neuronal metabolism in dementia [19]. On the other hand, however, it was shown that metabolites like lactate have a positive effect on the brain metabolism [20]. IHHT is well-tolerable and applicable to geriatric patients without any negative side effects [10] and has been shown to even improve exercise tolerance and aerobic capacity in patients without any additional exercises [21].…”