Devaux Jules B L, Hedges Christopher P, Birch Nigel, Herbert Neill, Renshaw Gillian M C, Hickey Anthony J R
School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Institute of Marine Science, The University Auckland, Auckland, New Zealand.
Front Physiol. 2019 Jan 18;9:1941. doi: 10.3389/fphys.2018.01941. eCollection 2018.
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 (). Mitochondrial respiration (JO) is required to generate an electrical gradient (ΔΨm) and a pH gradient to power ATP synthesis, yet the impact of pH modulation on brain 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 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 JO, ΔΨm, and H buffering capacities within permeabilized brain and swelling of isolated from non-permeabilized brains. We then measured ATP synthesis rates in the most HTS () and the HSS () at pH 7.25 and 6.65. Mitochondria from HTS brain did have greater H buffering capacities than HSS (∼10 mU pH.mg ). HTS swelled by 40% when exposed to a decrease of 1.5 pH units, and JO 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 inner-membrane, suggested that with acidosis, HTS may in part harness extra- 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, volumes and ΔΨm decreased downward pH 6.9 in HSS and paradoxically, JO 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 of these intertidal fish have adaptations that enhance ATP synthesis efficiency under acidic conditions such as those that occur in hypoxic or reoxygenated brain.
脊椎动物的大脑通常对酸中毒非常敏感，因此缺氧导致的pH值下降可能会对脑线粒体产生影响（）。线粒体呼吸（JO）是产生电化学梯度（ΔΨm）和pH梯度以驱动ATP合成所必需的，然而pH调节对脑功能的影响在很大程度上仍未得到探索。由于岩池中的潮间带鱼类经常经历缺氧和复氧过程，它们很可能会经历细胞pH值的变化。因此，我们比较了四种新西兰三鳍鱼，从潮间带耐缺氧物种（HTS）到潮下带缺氧敏感物种（HSS）。我们预测，在维持结构和功能方面，HTS比HSS更能耐受酸中毒。使用与荧光计和pH电极相连的呼吸计，我们滴定乳酸以降低培养基的pH值，并同时记录透化脑内的JO、ΔΨm和H缓冲能力，以及从非透化脑分离出的脑肿胀情况。然后，我们测量了最耐缺氧物种（HTS）和缺氧敏感物种（HSS）在pH 7.25和6.65时的ATP合成速率。HTS脑线粒体的H缓冲能力确实比HSS更大（约10 mU pH.mg）。当暴露于pH值下降1.5个单位时，HTS肿胀了40%，并且HTS中的JO最多降低了15%。然而，HTS能够将ΔΨm维持在接近 -120 mV。就跨内膜移动的电荷而言，功的估计表明，在酸中毒情况下，HTS可能部分利用额外的H来维持ΔΨm，因此能够支持ATP的产生。相对于pH 7.25，在pH 6.65时ATP合成速率升高和P:O比值增强证实了这一点。相比之下，在HSS中，体积和ΔΨm在pH值降至6.9以下时下降，而且矛盾的是，JO增加了（约25%），但在pH 6.65时ATP合成和P:O比值却降低了。这表明HSS在酸中毒时失去了偶联。总体而言，这些潮间带鱼类具有适应性，可在酸性条件下（如缺氧或复氧脑内出现的酸性条件）提高ATP合成效率。
