Biochimica et Biophysica Acta-Bioenergetics最新文献_第5页

Atypical absorption response to the trans-thylakoid electric field in the acidothermophilic red algae Cyanidioschyzon merolae and Galdieria partita 嗜酸嗜热红藻对类囊体反式电场的非典型吸收响应。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-02-07 DOI: 10.1016/j.bbabio.2025.149544

Guan-Lin Wu , Shin-Ying Tzeng , Benjamin Bailleul , Julien Sellés , You-Yuan Zhang , Han-Yi Fu

An absorption change responding to the change in the trans-thylakoid electric field (Δψ), also known as the electrochromic shift (ECS) signal, is widely used to probe multiple photosynthetic processes. The ECS signals either display a linear response of absorption changes to Δψ, independent of the trans-thylakoid electric field preexisting before actinic light (ψ_O), or a quadratic response, dependent on ψ_O. In the acidothermophilic red algae Cyanidioschyzon merolae and Galdieria partita, the absorption changes induced by single turnover saturating light flashes were affected by external pH. The effects of elevated external pH on the flash-induced absorption changes were explained by diminished ψ_O, as shown with the treatment of ionophores. We identified three contributions to the absorption changes: c-type cytochrome oxidized-minus-reduced signal and ECS signals showing both ψ_O-dependent and ψ_O-independent responses. Based on this, we could reveal that the effects of elevated external pH on the flash-induced absorption changes were due to variations of ψ_O, which in turn changed the contribution of the ψ_O-dependent ECS, as shown with the treatment of ionophores. Further analysis revealed that the ψ_O-dependent ECS signal exhibited a quadratic response to Δψ at low ψ_O, but the quadraticity was lost at higher ψ_O, providing insights for comprehending the atypical nature of the ECS signal. Our approach to identifying the ψ_O-dependent and ψ_O-independent ECS signals enables the ECS-based measurements for further investigation of the bioenergetics of electron and proton transport in red algae.

响应类囊体反式电场变化的吸收变化（Δψ），也称为电致变色位移（ECS）信号，被广泛用于探测多种光合作用过程。ECS信号要么显示吸收变化到Δψ的线性响应，独立于光化光之前存在的类囊体反式电场（ψO），要么显示二次响应，依赖于ψO。在嗜酸热的红藻紫藻（Cyanidioschyzon merolae）和红藻（Galdieria partita）中，单次翻转饱和闪光引起的吸收变化受外部pH值的影响，外部pH值升高对闪光引起的吸收变化的影响可以用离子团处理后的减ψO来解释。我们发现了三种对吸收变化的贡献：c型细胞色素氧化-减还原信号和ECS信号，它们同时表现出依赖于和不依赖于ψ o的响应。基于此，我们可以揭示，外部pH升高对闪致吸收变化的影响是由于ψO的变化，进而改变了依赖于ψO的ECS的贡献，如离子载体处理所示。进一步分析表明，依赖于ψO的ECS信号在低ψO时对Δψ表现出二次响应，但在高ψO时却失去了二次响应，这为理解ECS信号的非典型性质提供了见解。我们确定了依赖于和不依赖于ψ o的ECS信号的方法，使基于ECS的测量能够进一步研究红藻中电子和质子传输的生物能量学。

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引用次数: 0

Mutational interference with oligomerization properties of OCP-related apo- and holoproteins studied by analytical ultracentrifugation 突变干扰对ocp相关载脂蛋白和全蛋白寡聚化特性的研究。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI: 10.1016/j.bbabio.2025.149538

Anna Marta Koczula , Nils Cremer , Marcus Moldenhauer , Nikolai N. Sluchanko , Eugene G. Maksimov , Thomas Friedrich

In this study, the oligomerization pattern of apo- and holoforms of the Orange Carotenoid Protein (OCP) was examined under different conditions such as photoactivation state, concentration, and carotenoid embedment using analytical ultracentrifugation. Furthermore, studies were conducted on OCP constructs carrying point mutations of amino acid residues affecting OCP oligomerization. Our findings reveal that the concentration-dependent dimerization of dark-adapted OCP holoprotein from Synechocystis sp. PCC 6803 can be effectively prevented by the R27L mutation in the OCP-NTD. By introducing the E258R mutation (also in conjunction with R27L) into the OCP-CTD, monomeric OCP apoprotein can be obtained. Additionally, the holoprotein of the dark-adapted OCP-R27L/E258R variant was monomeric, and, supported by size-exclusion chromatography experiments, the photoactivated form of the OCP-R27L/E258R variant was monomeric as well. This variant, which does not oligomerize in either photocycle state, returns from the photoactivated to the dark-adapted state at a significantly faster rate than the OCP wild-type and the R27L mutant thereof. These observations also highlight the crucial interdependence between OCP dimerization in both photocycle states, the lifetime of the photoactive state of OCP, and the kinetics of the OCP photocycle.

在本研究中，利用超离心分析技术研究了橙类胡萝卜素蛋白（OCP）在不同的光活化状态、浓度和类胡萝卜素包埋等条件下的载脂蛋白和全型寡聚化模式。此外，还对携带影响OCP寡聚化的氨基酸残基点突变的OCP构建体进行了研究。我们的研究结果表明，Synechocystis sp. PCC 6803的暗适应OCP全蛋白的浓度依赖性二聚化可以通过OCP- ntd的R27L突变有效地阻止。通过将E258R突变（也与R27L一起）引入OCP- ctd，可以获得单体OCP载脂蛋白。此外，暗适应OCP-R27L/E258R变体的全蛋白是单体的，并且，通过尺寸排斥色谱实验，OCP-R27L/E258R变体的光激活形式也是单体的。该突变体在两种光循环状态下都不发生寡聚化，从光激活状态恢复到暗适应状态的速度明显快于OCP野生型及其R27L突变体。这些观察结果还强调了OCP在两种光循环状态下二聚化、OCP光活性状态的寿命和OCP光循环动力学之间的关键相互依赖性。

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引用次数: 0

Corrigendum to “Structural robustness of the NADH binding site in NADH: Ubiquinone oxidoreductase (complex I)” [Biochim. Biophys. Acta (BBA) – Bioenerg. (2024)/149491] “NADH中NADH结合位点的结构稳健性：泛醌氧化还原酶（复合体I）”的更正[Biochim。Biophys。学报（工商管理学士）-生物能源。(2024) / 149491)。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-02-14 DOI: 10.1016/j.bbabio.2025.149549

Sanaz Göppert-Asadollahpour, Daniel Wohlwend, Thorsten Friedrich

引用次数: 0

Clinical ischemia-reperfusion injury: Driven by reductive rather than oxidative stress? A narrative review 临床缺血再灌注损伤：由还原性而非氧化性应激驱动？叙述性评论

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1016/j.bbabio.2025.149539

Michèle J.C. de Kok , Alexander F.M. Schaapherder , Jonna R. Bloeme - ter Horst , Maria Letizia Lo Faro , Dorottya K. de Vries , Rutger J. Ploeg , Jaap A. Bakker , Jan H.N. Lindeman

Ischemia-reperfusion (IR) injury remains a major contributor to organ dysfunction following transient ischemic insults. Although numerous interventions have been found effective to reduce IR injury in preclinical models, none of these therapies have been successfully translated to the clinical setting. In the context of the persistent translational gap, we systematically investigated the mechanisms implicated in IR injury using kidney donation and transplantation as a clinical model of IR. Whilst our results do not implicate traditional culprits such as reactive oxygen species, complement activation or inflammation as triggers of IR injury, they reveal a clear metabolic signature for renal IR injury. This discriminatory signature of IR injury is consistent with a post-reperfusion metabolic paralysis and involves high-energy phosphate depletion, tricarboxylic acid cycle defects, and a compensatory activation of catabolic routes. Against this background, the picture emerges that clinical IR injury is driven by reductive stress. In this article, we therefore wish to elaborate on the processes contributing to reductive stress in the context of clinical IR injury and provide a better insight in potential clinical therapeutic strategies that might be helpful in restoring the redox balance.

缺血再灌注（IR）损伤仍然是短暂性缺血损伤后器官功能障碍的主要原因。尽管在临床前模型中发现许多干预措施可以有效地减少IR损伤，但这些治疗方法都没有成功地转化为临床环境。在持续翻译空白的背景下，我们系统地研究了涉及IR损伤的机制，使用肾脏捐赠和移植作为IR的临床模型。虽然我们的研究结果没有暗示传统的罪魁祸首，如活性氧、补体激活或炎症是IR损伤的触发因素，但它们揭示了肾脏IR损伤的明确代谢特征。IR损伤的这种歧视性特征与再灌注后代谢瘫痪相一致，涉及高能磷酸盐消耗、三羧酸循环缺陷和分解代谢途径的代偿激活。在此背景下，临床IR损伤是由还原性应激驱动的。因此，在这篇文章中，我们希望详细阐述在临床IR损伤的背景下有助于减少应激的过程，并为可能有助于恢复氧化还原平衡的潜在临床治疗策略提供更好的见解。

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引用次数: 0

Commentary: Why do many cell biology papers contain fundamental bioenergetic errors? 评论：为什么许多细胞生物学论文包含基本的生物能错误？

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1016/j.bbabio.2025.149541

David G. Nicholls

To professional bioenergeticists, the thermodynamic and kinetic constraints on mitochondrial function are self-evident. It is therefore profoundly concerning that high-profile cell biology papers continue to appear containing fundamental bioenergetic errors that appear to have evaded the scrutiny of the principal investigator, co-authors, editors and, apparently, at least some of the referees. The problem is not new, and seems to stem from a perception that bioenergetics is a ‘difficult’ subject, both at undergraduate level, if it is taught in any depth, and in research, where cell biologists are faced with biophysical concepts such as protonmotive force, ion flux, redox potential and Gibbs free energy.

对于专业的生物能量学家来说，线粒体功能的热力学和动力学约束是不言而喻的。因此，令人深感担忧的是，高调的细胞生物学论文继续出现，其中包含基本的生物能量错误，这些错误似乎逃避了首席研究员、共同作者、编辑，显然，至少是一些裁判的审查。这个问题并不新鲜，而且似乎源于这样一种观念，即生物能量学是一门“困难”的学科，无论是在本科阶段，如果深入教授的话，还是在研究中，细胞生物学家都面临着诸如质子动力、离子通量、氧化还原势和吉布斯自由能等生物物理概念。

引用次数: 0

Structural integrity and near-infrared absorption of the LH1 complex of Thermochromatium tepidum: Influence from the C-terminal lysine residues of LH1 α-polypeptide 温染菌LH1配合物的结构完整性和近红外吸收：LH1 α-多肽c端赖氨酸残基的影响

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-02-09 DOI: 10.1016/j.bbabio.2025.149545

Yi-Hao Yan , Yu-Qian Li , Mei-Juan Zou , Long-Jiang Yu , Jian-Ping Zhang

The light-harvesting complex 1-reaction center (LH1-RC) photosystem of the thermophilic purple sulfur bacterium Thermochromatium (Tch.) tepidum exhibits a near-infrared LH1-Q_y absorption band at 915 nm as regulated by binding calcium ions (Ca²⁺). To further explore the possible involvement of the C-terminal lysine residues of the LH1 α-polypeptide, we have genetically engineered a Rhodospirillum rubrum mutant strain to yield the site-directed modifications of the terminal α-Lys60 and α-Lys61 residues of Tch. tepidum LH1 α-polypeptide. Four of the LH1 mutants exhibit a subtle blue shift of 3 nm upon deletion or substitution of the lysine residues, however, they display over 40 nm blue shifts upon Ca²⁺ removal by ethylene diamine tetraacetic acid (EDTA) treatment. Spectral properties of native Tch. tepidum LH1-RC, the LH1-only, and the mutant LH1-only complexes are compared on a structural basis, which allows us to conclude that the C-terminal lysine residues and the Ca²⁺ binding synergistically affect the structural integrity and the LH1-Q_y spectral shift. This work demonstrates a methodology for the genetic manipulation of photosynthetic proteins lacking mutagenesis information, and may shed light on understanding the detailed structural factors involved in tuning the LH1-Q_y absorption.

嗜热紫色硫细菌Thermochromatium (Tch.) tepidum的集光配合物1-反应中心（LH1-RC）光系统在915 nm处表现出受钙离子（Ca2+）结合调控的近红外LH1-Qy吸收带。为了进一步探索LH1 α-多肽c端赖氨酸残基的可能参与，我们对红红螺旋菌突变株进行了基因工程改造，以获得Tch末端α-Lys60和α-Lys61残基的位点定向修饰。鳞片LH1 α-多肽。其中四个LH1突变体在赖氨酸残基缺失或取代后表现出3 nm的轻微蓝移，然而，在乙二胺四乙酸（EDTA）处理下去除Ca2+后，它们表现出超过40 nm的蓝移。天然Tch的光谱性质。在结构基础上比较了tepidum LH1-RC， LH1-only和突变体LH1-only复合物，这使我们可以得出结论，c端赖氨酸残基和Ca2+结合协同影响结构完整性和LH1-Qy谱移。这项工作展示了一种缺乏突变信息的光合蛋白的遗传操作方法，并可能有助于理解调节LH1-Qy吸收的详细结构因素。

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引用次数: 0

Interplay of acidic residues in the proton channel of E. coli cytochrome bd-I oxidase to promote oxygen reduction and NO release 大肠杆菌细胞色素bd-I氧化酶质子通道酸性残基促进氧还原和NO释放的相互作用。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-01-06 DOI: 10.1016/j.bbabio.2025.149537

Raaif Siddeeque , Lucia Heger , Jan Kägi , Thorsten Friedrich , Frédéric Melin , Petra Hellwig

The reduction of oxygen to water is crucial to life under aerobic conditions. Cytochrome bd oxidases perform this reaction with a very high oxygen affinity. Members of this protein family are solely found in prokaryotes and some archaea playing an important role in bacterial virulence and antibiotic resistance. Here, we combine mutagenesis, electrocatalysis, nitric oxide binding and release experiments as well as FTIR spectroscopy to demonstrate that proton delivery to the active site is essentially rate limiting in Cyt bd-I electrocatalysis. D58 and D105 of subunit CydB are crucial residues in this proton path and communicate via a hydrogen bond network. Oxygen reduction depends on proton delivery to the active site, which also influences NO release.

氧还原成水对有氧条件下的生命至关重要。细胞色素bd氧化酶以非常高的氧亲和力进行该反应。该蛋白家族成员仅存在于原核生物和一些古细菌中，在细菌毒力和抗生素耐药性中起重要作用。在这里，我们结合诱变、电催化、一氧化氮结合和释放实验以及FTIR光谱来证明质子传递到活性位点在Cyt bd-I电催化中基本上是限速的。CydB亚基的D58和D105是这条质子路径上的关键残基，并通过氢键网络进行通信。氧还原依赖于质子传递到活性部位，这也影响NO的释放。

引用次数: 0

The mitochondriotropic antioxidants AntiOxBEN2 and AntiOxCIN4 are structurally-similar but differentially alter energy homeostasis in human skin fibroblasts 线粒体抗氧化剂AntiOxBEN2和AntiOxCIN4结构相似，但改变人皮肤成纤维细胞的能量稳态存在差异。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-01-07 DOI: 10.1016/j.bbabio.2025.149535

José Teixeira , Sofia Benfeito , Rodrigo Carreira , André Barbosa , Ricardo Amorim , Ludgero C. Tavares , John G. Jones , Nuno Raimundo , Fernando Cagide , Catarina Oliveira , Fernanda Borges , Werner J.H. Koopman , Paulo J. Oliveira

Mitochondrial dysfunction and increased reactive oxygen species (ROS) generation play an import role in different human pathologies. In this context, mitochondrial targeting of potentially protective antioxidants by their coupling to the lipophilic triphenylphosphonium cation (TPP) is widely applied. Employing a six‑carbon (C₆) linker, we recently demonstrated that mitochondria-targeted phenolic antioxidants derived from gallic acid (AntiOxBEN₂) and caffeic acid (AntiOxCIN₄) counterbalance oxidative stress in primary human skin fibroblasts by activating ROS-protective mechanisms. Here we demonstrate that C₆-TPP (but not AntiOxBEN₂ and AntiOxCIN₄) induce cell death in human skin fibroblasts. This indicates that C₆-TPP cytoxocity is counterbalanced by the antioxidant moieties of AntiOxBEN₂ and AntiOxCIN₄. Remarkably, C₆-TPP and AntiOxBEN₂ (but not AntiOxCIN₄) induced a glycolytic switch, as exemplified by a reduced cellular oxygen consumption rate (OCR), increased extracellular acidification rate (ECAR), elevated extracellular lactate levels, and higher protein levels of glucose transporter 1 (GLUT-1). This switch involved activation of AMP-activated protein kinase (AMPK) and fully compensated for the loss in mitochondrial ATP production by sustaining cellular ATP content. When glycolytic switch induction was prevented (i.e. by using a glucose-free, galactose-containing medium), AntiOxBEN₂ induced cell death whereas AntiOxCIN₄ did not. We conclude that, despite their similar chemical structure and antioxidant capacity, AntiOxBEN₂ and AntiOxCIN₄ display both common (redox-adaptive) and specific (bioenergetic-adaptive) effects.

线粒体功能障碍和活性氧（ROS）生成增加在不同的人类病理中起重要作用。在这种情况下，线粒体靶向通过与亲脂性三苯基磷酸阳离子（TPP）偶联的潜在保护性抗氧化剂被广泛应用。利用六碳（C6）连接体，我们最近证明了线粒体靶向的酚类抗氧化剂来源于没食子酸（AntiOxBEN2）和咖啡酸（AntiOxCIN4），通过激活ros保护机制来平衡人皮肤成纤维细胞的氧化应激。在这里，我们证明C6-TPP（而不是抗oxben2和抗oxcin4）诱导人皮肤成纤维细胞死亡。这表明C6-TPP的细胞毒性被AntiOxBEN2和AntiOxCIN4的抗氧化部分所抵消。值得注意的是，C6-TPP和抗oxben2（而不是抗oxcin4）诱导糖酵解开关，如细胞耗氧率（OCR）降低，细胞外酸化率（ECAR）增加，细胞外乳酸水平升高，葡萄糖转运蛋白1 （GLUT-1）蛋白水平升高。这种转换涉及到amp激活的蛋白激酶（AMPK）的激活，并通过维持细胞ATP含量来完全补偿线粒体ATP产生的损失。当糖酵解开关诱导被阻止时（即使用不含葡萄糖、含半乳糖的培养基），抗oxben2诱导细胞死亡，而抗oxcin4则没有。我们得出结论，尽管它们具有相似的化学结构和抗氧化能力，AntiOxBEN2和AntiOxCIN4显示出共同（氧化还原适应）和特异性（生物能量适应）的作用。

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引用次数: 0

Engineering of thermal stability in the recombinant xanthorhodopsin from Salinibacter ruber 重组橡胶盐碱菌黄杉质热稳定性的工程研究

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2025-02-18 DOI: 10.1016/j.bbabio.2025.149547

Lada E. Petrovskaya , Vadim A. Bolshakov , Evgeniy P. Lukashev , Elena A. Kryukova , Eugene G. Maksimov , Andrei B. Rubin , Dmitriy A. Dolgikh , Sergei P. Balashov , Mikhail P. Kirpichnikov

Solubilization in detergents is a widely used technique for the isolation of membrane proteins and the study of their properties. Unfortunately, protein stability in detergent micelles can sometimes be compromised. We encountered this issue with xanthorhodopsin (XR) from Salinibacter ruber, which had been previously engineered for expression in Escherichia coli cells. To explore the factors affecting stability and to enhance thermal stability of recombinant XR preparations following solubilization of membranes using n-dodecyl-β-D-maltopyranoside and nickel-affinity chromatography, we developed a series of hybrid proteins based on the homology between XR and a stable rhodopsin from Gloeobacter violaceus (GR). Functional studies of these hybrids and measurements of their melting temperatures revealed the structural elements of XR that account for its notable difference in stability compared to GR, despite their high overall homology of approximately 50 % identical residues.

In particular, XR variants with an engineered loop between transmembrane helices D and E, similar to that in GR, demonstrated enhanced stability. However, we found that replacing the DE loop affects carotenoid binding. Additionally, two hybrid proteins containing the C and D helices from GR exhibited increased stability as well as improved photocycle and proton transport rates. In conclusion, we have demonstrated that optimizing the amino acid sequence of xanthorhodopsin from S. ruber based on its homology with Gloeobacter rhodopsin is an effective approach to enhance its thermal stability in vitro and improve its potential for optogenetic applications.

洗涤剂中的增溶是一种广泛应用于膜蛋白分离及其性质研究的技术。不幸的是，洗涤剂胶束中的蛋白质稳定性有时会受到损害。我们在使用来自橡胶盐碱杆菌的XR时遇到了这个问题，XR先前被设计用于在大肠杆菌细胞中表达。为了探索影响XR稳定性的因素，并利用n-十二烷基-β- d -麦芽吡喃苷和镍亲和层析法提高膜增溶后重组XR制剂的热稳定性，我们基于XR与Gloeobacter violaceus （GR）中稳定的紫红质的同源性，开发了一系列杂交蛋白。对这些杂合体的功能研究和熔融温度的测量揭示了XR的结构元素，这些结构元素解释了XR与GR相比稳定性的显著差异，尽管它们的总体同源性约为50%相同的残基。特别是，在跨膜螺旋D和E之间带有工程环的XR变异，与GR相似，表现出更高的稳定性。然而，我们发现替换DE环会影响类胡萝卜素的结合。此外，含有GR的C和D螺旋的两种杂交蛋白表现出更高的稳定性，并改善了光循环和质子运输速率。综上所述，基于与Gloeobacter rhodopsin的同源性，优化橡胶树黄紫质的氨基酸序列是提高其体外热稳定性和光遗传学应用潜力的有效途径。

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引用次数: 0

Species differences in glycerol-3-phosphate metabolism reveals trade-offs between metabolic adaptations and cell proliferation 甘油-3-磷酸代谢的物种差异揭示了代谢适应和细胞增殖之间的权衡。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-04-01 Epub Date: 2024-12-02 DOI: 10.1016/j.bbabio.2024.149530

Kateryna Gaertner , Mügen Terzioglu , Craig Michell , Riikka Tapanainen , Jaakko Pohjoismäki , Eric Dufour , Sina Saari

The temperate climate-adapted brown hare (Lepus europaeus) and the cold-adapted mountain hare (Lepus timidus) are closely related and interfertile species. However, their skin fibroblasts display distinct gene expression profiles related to fundamental cellular processes. This indicates important metabolic divergence between the two species. Through targeted metabolomics and metabolite tracing, we identified species-specific variations in glycerol 3-phosphate (G3P) metabolism. G3P is a key metabolite of the G3P shuttle, which transfers reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain (ETC), consequently regulating glycolysis, lipid metabolism, and mitochondrial bioenergetics. Alterations in G3P metabolism have been implicated in multiple human pathologies including cancer and diabetes. We observed that mountain hare mitochondria exhibit elevated G3P shuttle activity, alongside increased membrane potential and decreased mitochondrial temperature. Silencing mitochondrial G3P dehydrogenase (GPD2), which couples the conversion of G3P to the ETC, uncovered its species-specific role in controlling mitochondrial membrane potential and highlighted its involvement in skin fibroblast thermogenesis. Unexpectedly, GPD2 silencing enhanced wound healing and cell proliferation rates in a species-specific manner. Our study underscores the pivotal role of the G3P shuttle in mediating physiological, bioenergetic, and metabolic divergence between these hare species.

温带适应的褐兔（Lepus europaeus）和寒冷适应的山地兔（Lepus timidus）是亲缘关系密切的杂交物种。然而，他们的皮肤成纤维细胞显示出与基本细胞过程相关的不同基因表达谱。这表明两个物种之间存在重要的代谢差异。通过靶向代谢组学和代谢物追踪，我们确定了甘油3-磷酸（G3P）代谢的物种特异性变化。G3P是G3P穿梭的关键代谢物，它将还原性等价物从胞质NADH转移到线粒体电子传递链（ETC），从而调节糖酵解、脂质代谢和线粒体生物能量学。G3P代谢的改变与包括癌症和糖尿病在内的多种人类疾病有关。我们观察到，山梨线粒体G3P穿梭活性升高，同时膜电位升高，线粒体温度降低。沉默线粒体G3P脱氢酶（GPD2），发现其在控制线粒体膜电位中的物种特异性作用，并强调其参与皮肤成纤维细胞产热。GPD2将G3P转化为ETC偶联。出乎意料的是，GPD2沉默以物种特异性的方式增强了伤口愈合和细胞增殖率。我们的研究强调了G3P穿梭在调节这些物种之间的生理、生物能量和代谢差异中的关键作用。

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引用次数: 0