Tissue-specific seasonal changes in mitochondrial function of a mammalian hibernator
Tissue-specific seasonal changes in mitochondrial function of a mammalian hibernator
复制标题
DOI：
10.1152/ajpregu.00427.2016
复制
发表时间：
2017-08-01
影响因子：
2.8
通讯作者：
Chicco, Adam J.
中科院分区：
文献类型：
--
作者：
Heim, Ashley B.;Chung, Dillon;Chicco, Adam J.
冬眠的哺乳动物，如金毛地松鼠（callospermoophilus lateral； GMGS），在冬季停止进食，同时降低代谢率和体温，完全依靠冬眠前储存的内源性燃料生存。我们假设线粒体，氧化代谢的细胞位点，在碳水化合物和脂肪酸的利用上经历了组织特异性的季节性调整，以促进或补充这种显着的表型。为了解决这个问题，我们使用多底物滴定法对夏季（活动）、秋季（冬眠前）和冬季（冬眠）季节从GMGS肝脏、心脏、骨骼肌和棕色脂肪组织（BAT）中分离的线粒体进行了高分辨率呼吸测定。线粒体磷脂组成被认为是跨组织和季节呼吸功能的内在调节剂。呼吸测量揭示了线粒体氧化磷酸化能力、底物利用和偶联效率的季节性变化，反映了它们所支持的组织的不同功能和代谢需求。跨组织的一致发现是脂肪酸（棕榈酰肉碱）对冬眠前和冬眠季节呼吸参数的影响更大。特别是，脂肪酸对心脏、肌肉和肝脏线粒体中丙酮酸支持的氧化磷酸化有更大的抑制作用，并在寒冷的季节增强BAT和肌肉线粒体的非偶联呼吸。线粒体膜组成的季节性变化反映了多不饱和脂肪酸供应和利用的变化，但通常是温和的，与功能变化不一致。总之，线粒体以一种组织特异性的方式响应身体活动、温度和营养可用性的季节性变化，补充了哺乳动物冬眠时生物能量和温度调节需求的周期性变化。
Mammalian hibernators, such as golden-mantled ground squirrels (Callospermophilus lateralis; GMGS), cease to feed while reducing metabolic rate and body temperature during winter months, surviving exclusively on endogenous fuels stored before hibernation. We hypothesized that mitochondria, the cellular sites of oxidative metabolism, undergo tissue-specific seasonal adjustments in carbohydrate and fatty acid utilization to facilitate or complement this remarkable phenotype. To address this, we performed high-resolution respirometry of mitochondria isolated from GMGS liver, heart, skeletal muscle, and brown adipose tissue (BAT) sampled during summer (active), fall (prehibernation), and winter (hibernation) seasons using multisubstrate titration protocols. Mitochondrial phospholipid composition was examined as a postulated intrinsic modulator of respiratory function across tissues and seasons. Respirometry revealed seasonal variations in mitochondrial oxidative phosphorylation capacity, substrate utilization, and coupling efficiency that reflected the distinct functions and metabolic demands of the tissues they support. A consistent finding across tissues was a greater influence of fatty acids (palmitoylcarnitine) on respiratory parameters during the prehibernation and hibernation seasons. In particular, fatty acids had a greater suppressive effect on pyruvate-supported oxidative phosphorylation in heart, muscle, and liver mitochondria and enhanced uncoupled respiration in BAT and muscle mitochondria in the colder seasons. Seasonal variations in the mitochondrial membrane composition reflected changes in the supply and utilization of polyunsaturated fatty acids but were generally mild and inconsistent with functional variations. In conclusion, mitochondria respond to seasonal variations in physical activity, temperature, and nutrient availability in a tissue-specific manner that complements circannual shifts in the bioenergetic and thermoregulatory demands of mammalian hibernators.