Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
WIREs Mech Dis. 2022 Sep;14(5):e1569. doi: 10.1002/wsbm.1569. Epub 2022 Jun 9.
Mammalian sperm, the only cells that achieve their purpose outside their organism of origin, have to swim vigorously within the female reproductive tract to reach an oocyte. Flagellar dyneins drive sperm motility, which accounts for the consumption of high amounts of ATP. The two main ATP-producing metabolic pathways are compartmentalized in sperm: oxidative phosphorylation in the midpiece and glycolysis in the principal piece. The relative preponderance of these pathways has been discussed for decades (the so-called sperm energy debate). The debate has been muddled by species-specific variances and by technical constraints. But recent findings suggest that sperm from most mammalian species employ a versatile metabolic strategy to maintain motility according to the physiological environment. Different metabolic pathways likely coordinate by using exogenous and/or endogenous substrates in order to produce ATP efficiently. Defects in any of these pathways (glycolysis, mitochondrial oxidative phosphorylation, Krebs cycle, fatty acids oxidation, and ketone bodies oxidation, among others) may disturb sperm motility and be at the origin of male infertility. Understanding sperm bioenergetics is thus crucial for building new diagnostic tools, and for the development of treatments for patients presenting with low sperm motility. Some of these patients may benefit from personalized metabolic supplementations and dietary interventions. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology.
哺乳动物精子是唯一在其起源生物体之外实现其目的的细胞,必须在雌性生殖道内剧烈游动才能到达卵子。鞭毛动力蛋白驱动精子运动,这消耗了大量的三磷酸腺苷(ATP)。两种主要的产生 ATP 的代谢途径在精子中被分隔开:中段的氧化磷酸化和主段的糖酵解。几十年来,人们一直在讨论这些途径的相对优势(所谓的精子能量争论)。这个争论被物种特异性差异和技术限制所混淆。但最近的发现表明,大多数哺乳动物的精子采用了一种通用的代谢策略,根据生理环境来维持运动能力。不同的代谢途径可能通过使用外源性和/或内源性底物来协调,以有效地产生 ATP。这些途径中的任何缺陷(糖酵解、线粒体氧化磷酸化、三羧酸循环、脂肪酸氧化和酮体氧化等)都可能扰乱精子运动,并导致男性不育。因此,了解精子的生物能量学对于构建新的诊断工具以及为运动能力低下的患者开发治疗方法至关重要。其中一些患者可能受益于个性化的代谢补充和饮食干预。本文属于以下类别:生殖系统疾病 > 分子和细胞生理学。