Biochimica et Biophysica Acta-Bioenergetics最新文献_第2页

The internal alternative NADH dehydrogenase (Ndi1) is the electron input in the Saccharomyces cerevisiae respirasome 内部替代NADH脱氢酶（Ndi1）是酿酒酵母菌呼吸体的电子输入。

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-11-22 DOI: 10.1016/j.bbabio.2025.149574

Italo Lorandi , José Alfredo Hernández-Zúñiga , Mercedes Esparza-Perusquía , Genaro Matus-Ortega , Héctor Vázquez-Meza , Héctor Flores-Herrera , Juan Pablo Pardo , Federico Martínez , Oscar Flores-Herrera

Complex I is absent in mitochondria from Saccharomyces cerevisiae; instead, three rotenone-insensitive NADH dehydrogenases are present: two on the external (Nde1 and Nde2) and one on the internal (Ndi1) leaf of the inner mitochondrial membrane. In a previous work (1), we reported the presence of a supercomplex in S. cerevisiae constituted by the Ndi1 and complexes III₂ and IV with an apparent MW of 1600 kDa. In this work, respirasomes from WT and NDE1Δ/NDE2Δ strains were isolated, and their activities characterized. Kinetic characterization of NADH:DBQ oxidoreductase activity from respirasomes, as well as free Ndi1, showed V_max values of 0.85 ± 0.01, 0.82 ± 0.02, and 0.51 ± 0.02 μmol NADH oxidized·min⁻¹·mg⁻¹ for WT respirasome, NDE1Δ/NDE2Δ respirasome, and free Ndi1, respectively. The kinetic model for WT- and NDE1Δ/NDE2Δ respirasome was a Ping Pong Bi-Bi mechanism with two different stable enzyme forms, free (E) and modified enzyme (F); while the free Ndi1 exhibited a Random Bi-Bi mechanism with the ternary complex NADH-Ndi1-ubiquinone. This suggests that the interaction of Ndi1 with complexes III₂ and IV in the respirasome modifies its kinetic mechanism. Oxygen consumption values were 0.35 ± 0.07 and 0.34 ± 0.07 μmol O₂·min⁻¹·mg⁻¹ for WT and NDE1Δ/NDE2Δ respirasomes, respectively. The values for NADH/O₂ ratio were 2.4 ± 1.4 and 2.4 ± 1.6 for WT and NDE1Δ/NDE2Δ respirasomes, respectively, suggesting that electron flux from NADH to oxygen occurs in the S. cerevisiae respirasome. The electron transfer from NADH to oxygen was inhibited by flavone, antimycin A, or cyanide, but the NADH dehydrogenase activity of the respirasome was insensitive to antimycin A or cyanide, indicating that no codependence of respirasomal-Ndi1 activity occurs as reported in the Ustilago maydis respirasome. This result indicates that the activity of respirasomal Ndi1 may contribute to the quinol pool with no evidence of direct substrate channeling. This is the first evidence of the Ndi1 role as the electron input in the respirasome from S. cerevisiae.

在酿酒酵母的线粒体中不存在复合体I；相反，存在三个鱼藤酮不敏感的NADH脱氢酶：两个在线粒体内膜的外叶（Nde1和Nde2），一个在内叶（Ndi1）。在之前的工作(1)中，我们报道了在酿酒酵母中存在一个由Ndi1和配合物III2和IV组成的超配合物，其表观分子量为1600 kDa。本研究分离了WT和NDE1Δ/NDE2Δ菌株的呼吸小体，并对其活性进行了表征。NADH:DBQ氧化还原酶活性和游离Ndi1的动力学表征表明，WT、NDE1Δ/NDE2Δ和游离Ndi1的Vmax分别为0.85±0.01、0.82±0.02和0.51±0.02 μmol NADH氧化·min-1·mg-1。WT-和NDE1Δ/NDE2Δ呼吸酶体的动力学模型为两种不同的稳定酶形式——游离酶(E)和修饰酶(F)——的乒乓比比机制；而游离Ndi1则与nadh -Ndi1-泛醌的三元配合物表现出随机BiBi机制。这表明Ndi1与呼吸小体中的配合物III2和IV的相互作用改变了其动力学机制。WT和NDE1Δ/NDE2Δ呼吸小体的耗氧量分别为0.35±0.07和0.34±0.07 μmol O2·min-1·mg-1。WT和NDE1Δ/NDE2Δ呼吸小体的NADH/O2比值分别为2.4±1.4和2.4±1.6，说明NADH到氧的电子通量发生在酵母呼吸小体中。黄酮、抗霉素A或氰化物均能抑制NADH向氧的电子转移，但呼吸小体的NADH脱氢酶活性对抗霉素A或氰化物不敏感，这表明在麦氏黑穗病菌呼吸小体中没有报道的呼吸小体- ndi1活性的相互依赖。这一结果表明，呼吸小体Ndi1的活性可能在没有直接底物通道的情况下参与了喹啉池的形成。这是第一个证明Ndi1在酿酒链球菌呼吸小体中作为电子输入的证据。

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引用次数: 0

Increase in spillover and excitation energy dissipation during wet–dry transitions in the desert green alga Chlorella ohadii 沙漠绿藻奥哈地小球藻干湿转换过程中外溢和激发能耗散的增加。

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-09-17 DOI: 10.1016/j.bbabio.2025.149573

Soma Kawamura , Makio Yokono , Chiyo Noda , Jun Minagawa

•
Under drought, lack of an electron source (water) reduces the capacity of oxygen-evolving photosynthesis.
•
Consequently, even under low light, excess excitation energy may be generated, which is harmful as it leads to generation of reactive oxygen species.
•
When the desert green alga Chlorella ohadii undergoes desiccation, first photosystem II binds to photosystem I via LHCII to establish energy transfer pathways, and then excitation energy dissipation induced by a quencher is initiated.
•
This strategy may provide efficient protection of the entire photosynthetic apparatus during early stages of desiccation, when the available quencher may be insufficient.

•在干旱情况下，缺乏电子源（水）会降低进化氧气的光合作用的能力。•因此，即使在弱光下，也可能产生多余的激发能，这是有害的，因为它会导致活性氧的产生。•沙漠绿藻小球藻（Chlorella ohadii）在干燥过程中，首先光系统II通过LHCII与光系统I结合，建立能量传递途径，然后启动猝灭剂诱导的激发能量耗散。•这种策略可以在干燥的早期阶段为整个光合机构提供有效的保护，此时可用的猝灭剂可能不足。

引用次数: 0

Mechanism of Na+ ions contribution to the generation and maintenance of a high inner membrane potential in mitochondria Na+离子对线粒体高内膜电位产生和维持的作用机制

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-09-04 DOI: 10.1016/j.bbabio.2025.149571

Victor V. Lemeshko

A recent revision of the chemiosmotic theory was reported by Hernansanz-Agustín and coauthors as a discovery that a Na⁺ gradient across the mitochondrial inner membrane equates with the H⁺ gradient and contributes up to half of the inner membrane potential, without an explanation of the possible underlying mechanism. Based on the experimental data of these and other authors, and performed biophysical estimations, I propose a mechanism by which both the reported fast-acting Na⁺/H⁺ exchanger, associated with the complex I of the respiratory chain, and Na⁺ electrodiffusion in the intracristae space and the matrix allow maintenance of a high membrane potential.

最近，Hernansanz-Agustín及其合作者对化学渗透理论进行了修订，发现线粒体内膜上的Na+梯度与H+梯度相等，并贡献了高达一半的内膜电位，但没有解释可能的潜在机制。基于这些和其他作者的实验数据，并进行了生物物理估计，我提出了一种机制，通过这种机制，与呼吸链复合体I相关的快速Na+/H+交换剂和骨裂内空间和基质中的Na+电扩散可以维持高膜电位。

引用次数: 0

Vibrational cooling of monomeric bacteriochlorophylls in reaction centers of purple bacteria studied by time-resolved fluorescence spectroscopy 用时间分辨荧光光谱法研究了紫色细菌反应中心中单体细菌叶绿素的振动冷却

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-08-25 DOI: 10.1016/j.bbabio.2025.149570

Andrei G. Yakovlev , Alexandra S. Taisova

Photosynthesis in bacteria, algae, and plants begins with the absorption of light energy by (bacterio)chlorophyll molecules, part of which is then converted into heat, leading to a transient change in molecular temperature. We investigated this phenomenon in reaction centers (RCs) of the purple bacterium Rhodobacter (Rba.) sphaeroides using picosecond fluorescence spectroscopy. Exclusion of charge separation processes using the VR(L157) mutation allowed us to record the spectral dynamics of fluorescence of monomeric BChl a molecules. We found that excitation of RCs into the Soret band results in significant heating of BChl a by ~160 K with subsequent vibrational cooling, which manifests itself in a dynamic narrowing of the BChl a fluorescence spectrum with two characteristic times of 5 and 16 ps. The weaker heating by ~65 K and cooling with a characteristic time of 7.5 ps are observed upon excitation of RCs into the Q_x band. Excitation into the Q_у band does not result in any noticeable heating of BChl a. Difference absorption spectroscopy of tryptophan in the 280 nm region showed that the observed dynamics of the BChl a fluorescence spectrum are not associated with the dielectric rearrangement of the RCs protein matrix. Analysis of the obtained data using the phenomenological model of vibrational cooling led to the conclusion that during heat diffusion from excited BChl a, several amino acid residues from the immediate environment of BChl a act as the first solvation shell (FSS). At the first, faster stage, heat is transferred from BChl a to FSS, and at the second stage, FSS transfers heat to the protein matrix of RCs. Our work has shown the importance of taking into account vibrational cooling when studying the primary processes of photosynthesis.

细菌、藻类和植物的光合作用始于（细菌）叶绿素分子对光能的吸收，其中一部分光能随后转化为热量，导致分子温度的短暂变化。利用皮秒荧光光谱技术研究了球形红杆菌（Rba.）反应中心（RCs）的这一现象。利用VR（L157）突变排除电荷分离过程，使我们能够记录单体BChl a分子的荧光光谱动力学。我们发现，RCs激发到Soret波段后，BChl a会被~160 K显著加热，随后进行振动冷却，这表现为BChl a荧光光谱的动态变窄，特征时间为5和16 ps。RCs激发到Qx波段时，观察到~65 K的微弱加热和特征时间为7.5 ps的冷却。在280 nm区域色氨酸的差异吸收光谱显示，观察到的BChl a荧光光谱的动态与RCs蛋白基质的介电重排无关。利用振动冷却的现象学模型对得到的数据进行分析，得出在受激BChl a的热扩散过程中，来自BChl a直接环境的几个氨基酸残基充当第一溶剂化壳层（FSS）的结论。在第一阶段，热量从BChl a传递给FSS，在第二阶段，FSS将热量传递给RCs的蛋白质基质。我们的工作表明，在研究光合作用的主要过程时，考虑振动冷却的重要性。

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引用次数: 0

Photodamage and excitation energy quenching in PSII: A time-resolved fluorescence study in Arabidopsis 拟南芥PSII的光损伤和激发能猝灭：一个时间分辨荧光研究。

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-08-11 DOI: 10.1016/j.bbabio.2025.149569

Cleo Bagchus , Herbert van Amerongen , Emilie Wientjes

Photosynthesis is driven by light absorbed in photosystem (PS) I and II. Paradoxically, light can also inactivate photosynthesis, mainly by damage to PSII. The light-dependent decrease in functional PSII, referred to as photoinhibition, is initially accompanied by an increase of excitation quenching, energy dissipation characterized by a decline in the lifetime and yield of chlorophyll fluorescence. In plants, research has not yet been performed on the effect of photoinhibition on the fluorescence lifetime of PSII in conditions where the PSII reaction centers are closed or remain open (capable of performing photochemistry).

In this work, we studied the effect of photoinhibition on the fluorescence lifetime of PSII in Arabidopsis thaliana using time-resolved fluorescence measurements with a streak-camera setup in both closing (F_m) and non-closing (F_o) conditions. Measurements under F_m conditions in the chlorina mutant, lacking peripheral antenna, demonstrate formation of a photoinhibitory quencher in the PSII core complex. In F_o_, the average fluorescence lifetime of PSII increases upon induction of photoinhibition. This could be due to the degradation of quenched PSII core reaction center protein by FtsH proteases, which leads to unquenched and dysfunctional PSII. We tested this hypothesis by comparing WT plants with the FtsH2 lacking mutant. Based on the similar behavior, we conclude that degradation by FtsH proteases is not the main cause of the increase. Instead this increase is caused by the larger antenna size of still functional PSII. These findings provide new insights into the impact of photoinhibition on the PSII fluorescence lifetime in A. thaliana.

光合作用是由光系统I和II吸收的光驱动的。矛盾的是，光也可以使光合作用失活，主要是通过损害PSII。功能性PSII的光依赖性下降，称为光抑制，最初伴随着激发猝灭和能量耗散的增加，其特征是叶绿素荧光的寿命和产量下降。在植物中，在PSII反应中心关闭或保持开放（能够进行光化学反应）的条件下，光抑制对PSII荧光寿命的影响尚未进行研究。在这项工作中，我们研究了光抑制对拟南芥PSII荧光寿命的影响，利用条纹相机装置在关闭（Fm）和非关闭（Fo）条件下进行了时间分辨荧光测量。在Fm条件下对缺乏外围天线的氯突变体的测量表明，在PSII核心复合物中形成了光抑制猝灭剂。在Fo中，PSII的平均荧光寿命随着光抑制的诱导而增加。这可能是由于被淬灭的PSII核心反应中心蛋白被FtsH蛋白酶降解，从而导致未淬灭和功能失调的PSII。我们通过比较WT植株和缺乏FtsH2的突变体来验证这一假设。基于类似的行为，我们得出结论，FtsH蛋白酶的降解不是增加的主要原因。相反，这种增加是由仍然有效的PSII的较大天线尺寸引起的。这些发现为研究光抑制对拟南芥PSII荧光寿命的影响提供了新的见解。

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引用次数: 0

Chamber oxygen concentration impacts mitochondrial function and hydrogen peroxide appearance in permeabilized human skeletal muscle fibers 室内氧浓度影响线粒体功能和过氧化氢的外观在渗透人骨骼肌纤维

IF 2.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-08-11 DOI: 10.1016/j.bbabio.2025.149568

Bradley A. Ruple , Soung Hun Park , Jesse C. Craig , Matthew T. Lewis , Joel D. Trinity , Russell S. Richardson , Ryan M. Broxterman

Skeletal muscle mitochondrial respiration is commonly assessed ex vivo using permeabilized fibers in media with high oxygen (O₂) concentrations to ensure that O₂ availability does not limit respiration. However, high O₂ concentrations also increase the production of reactive O₂ species that can negatively affect respiration. In this study, we tested the hypotheses that permeabilized fiber mitochondria in a high, compared to low, O₂ concentration would (i) not be different at maximal state 3 respiration rate (V_max), (ii) have lower submaximal respiration rates at submaximal O₂ concentrations, and (iii) have greater total cumulative hydrogen peroxide (H₂O₂) appearance. We continuously monitored mitochondrial state 3 respiration and H₂O₂ appearance rates using high-resolution respirometry in permeabilized skeletal muscle fibers (12 untrained participants; 22 ± 4 yrs) with either control (~127 mmHg; CON) or high (~327 mmHg; HIGH) partial pressures of O₂ (PO₂). V_max was not different between conditions (HIGH: 80.7 ± 16.7 vs. CON: 82.3 ± 18.7 pmol/s/mg, p = 0.695). The PO₂ at 80 % V_max (P₈₀) was greater in HIGH (73.9 ± 25.5 vs. 28.0 ± 7.1 mmHg, p < 0.001) and respiration rates at 5–60 mmHg PO₂ were lower for HIGH than CON (all p < 0.001). Additionally, the total cumulative H₂O₂ appearance was greater in HIGH than CON (n = 11; 51.5 ± 23.2 vs. 18.3 ± 10.3 pmol/mg, p < 0.001), and this difference was directly correlated with the difference in P₈₀ (r = 0.655, p = 0.029). The current findings support that a high O₂ concentration, by itself, does not appear to affect V_max in the permeabilized skeletal muscle fiber preparation, but the corollary increase in H₂O₂ exposure may diminish mitochondrial state 3 respiratory function.

骨骼肌线粒体呼吸通常在高氧（O2）浓度的培养基中使用渗透性纤维进行体外评估，以确保O2的可用性不会限制呼吸。然而，高浓度的氧气也会增加活性氧的产生，从而对呼吸产生负面影响。在本研究中，我们测试了以下假设：与低氧浓度相比，高氧浓度下的通透性纤维线粒体(i)在最大状态3呼吸速率（Vmax）下没有差异，（ii）在次最大O2浓度下具有较低的次最大呼吸速率，以及（iii）具有更大的过氧化氢（H2O2）总累积量。我们在渗透骨骼肌纤维中使用高分辨率呼吸仪连续监测线粒体状态3呼吸和H2O2出现率(12名未经训练的参与者；22±4年)，对照组(~127 mmHg；CON)或高(~327 mmHg；高)分压O2 （PO2）。不同条件下Vmax无差异（HIGH: 80.7±16.7 vs CON: 82.3±18.7 pmol/s/mg, p = 0.695）。80% Vmax时的PO2 （P80）在HIGH组更高(73.9±25.5比28.0±7.1 mmHg, p <；0.001)， 5-60 mmHg PO2下HIGH组的呼吸速率低于CON组(p <；0.001)。此外，HIGH组H2O2总累积量大于CON组(n = 11；51.5±23.2 vs 18.3±10.3 pmol/mg, p <；0.001)，这一差异与P80的差异直接相关（r = 0.655, p = 0.029）。目前的研究结果支持，高浓度的O2本身似乎并不影响渗透性骨骼肌纤维制备中的Vmax，但H2O2暴露的必然增加可能会降低线粒体状态3呼吸功能。

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引用次数: 0

Deletion of AC8 in glioma cells elevates oxidative phosphorylation by system-wide remodeling of the mitochondrial proteome 胶质瘤细胞中AC8的缺失通过线粒体蛋白质组的全系统重塑提高氧化磷酸化。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-07-14 DOI: 10.1016/j.bbabio.2025.149567

Emil Jakobsen , Jacob M. Bech , Jens V. Andersen , Emil W. Westi , Martin R. Larsen , Niels H. Skotte , José M.A. Moreira , Blanca I. Aldana , Lasse K. Bak

The Warburg effect is the reprogramming of cancer cells towards glycolytic metabolism, likely producing and releasing lactate into the tumor microenvironment. This lactate has been suggested to partly drive tumor growth by signaling through the lactate receptor, GPR81. Thus, reprogramming cancer cells away from glycolytic activity may be beneficial for cancer treatment. Here, we show that deletion of ADCY8 (coding for adenylyl cyclase 8; AC8) employing the CRISPR-Cas9 technology in U87MG glioma cells, changes the proteome of these cells through a system-wide transformation in expression of mitochondrial proteins. These changes shift the metabolic balance towards oxidative phosphorylation, as shown by an increase in oxygen consumption, an elevation in tricarboxylic acid cycle flux, and a concomitant decrease in glycolytic flux. This metabolic shift is likely driven by the absence of AC8-mediated transcriptional regulation and may suggest that inhibition of AC8 activity could hold therapeutic potential in the treatment of cancer.

Warburg效应是癌细胞对糖酵解代谢的重编程，可能产生并释放乳酸到肿瘤微环境中。这种乳酸被认为通过乳酸受体GPR81信号传导部分驱动肿瘤生长。因此，重新编程癌细胞使其远离糖酵解活性可能对癌症治疗有益。在这里，我们发现ADCY8（编码腺苷酸环化酶8）的缺失；AC8)在U87MG胶质瘤细胞中采用CRISPR-Cas9技术，通过线粒体蛋白表达的全系统转化改变了这些细胞的蛋白质组。这些变化使代谢平衡转向氧化磷酸化，表现为耗氧量增加、三羧酸循环通量升高以及伴随的糖酵解通量减少。这种代谢转变可能是由于缺乏AC8介导的转录调节所驱动的，这可能表明抑制AC8活性在治疗癌症方面具有治疗潜力。

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引用次数: 0

Dynamic binding of acetogenin-type inhibitors to mitochondrial complex I revealed by photoaffinity labeling 通过光亲和标记揭示醋酸原型抑制剂与线粒体复合体I的动态结合。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-06-29 DOI: 10.1016/j.bbabio.2025.149566

Misaki Nishida , Cristina Pecorilla , Takahiro Masuya , Keitaro Hirano , Masato Abe , Oleksii Zdorevskyi , Vivek Sharma , Hideto Miyoshi , Masatoshi Murai

Acetogenins isolated from the Annonaceae plant family are potent inhibitors of mitochondrial NADH-ubiquinone (UQ) oxidoreductase (complex I). Since acetogenins have a markedly different chemical framework from other complex I inhibitors, studying their inhibitory action offers valuable insights into the mechanism of complex I inhibition. A cryo-EM structure of mouse complex I with a bound ~35 Å-long acetogenin derivative suggested that acetogenins bind along the full length of the predicted UQ-accessing tunnel, with their γ-lactone ring orientating toward the iron‑sulfur cluster N2. However, this binding mode does not fully explain the structure–activity relationships of various acetogenin derivatives. To further elucidate their inhibition mechanism, we conducted photoaffinity labeling experiments in bovine heart SMPs using a photoreactive acetogenin derivative DLA-1, containing a small photolabile diazirine near the γ-lactone ring. DLA-1 labeled both the complex I subunits 49-kDa and ND1, which define the architecture of “top” and “bottom” regions of the canonical UQ-accessing tunnel, respectively. Proteomic analysis revealed that the labeled sites in ND1 are not within the tunnel's interior, whereas in the case of 49-kDa subunit, part of the tunnel's inner region is labeled. To investigate the molecular basis of acetogenin binding, we performed atomistic molecular dynamics simulations of DLA-1 and a natural-type acetogenin analog in the UQ-accessing tunnel. The simulation data indicate that DLA-1 is relatively rigid yet adopts multiple conformations and interacts with several regions in the tunnel including the residues identified by photoaffinity labeling. Based on these results, we discuss the binding modes of acetogenin analogs to complex I.

从番荔枝科植物家族中分离出来的乙酰素是线粒体nadh -泛醌（UQ）氧化还原酶（复合体I）的有效抑制剂。由于acetogenins与其他复合物I抑制剂具有明显不同的化学框架，研究它们的抑制作用为复合物I抑制的机制提供了有价值的见解。结合~35 Å-long乙酰原蛋白衍生物的小鼠配合物I的低温电镜结构表明，乙酰原蛋白沿着预测的uq通道的全长结合，其γ-内酯环指向铁硫簇N2。然而，这种结合模式并不能完全解释各种醋酸原蛋白衍生物的构效关系。为了进一步阐明它们的抑制机制，我们在牛心脏SMPs中进行了光亲和标记实验，使用光反应性乙酰原素衍生物DLA-1，在γ-内酯环附近含有一个小的光可性重氮嘧啶。DLA-1标记了复合体I亚基49-kDa和ND1，它们分别定义了规范uq访问隧道的“顶部”和“底部”区域的结构。蛋白质组学分析显示，ND1中的标记位点不在隧道内部，而在49-kDa亚基的情况下，隧道内部区域的一部分被标记。为了研究乙酰源蛋白结合的分子基础，我们在uq通道中对DLA-1和天然乙酰源蛋白类似物进行了原子分子动力学模拟。模拟数据表明，DLA-1相对刚性，但具有多种构象，并与隧道中的多个区域相互作用，包括光亲和标记识别的残基。基于这些结果，我们讨论了醋酸原类似物与配合物I的结合模式。

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引用次数: 0

Human VDAC3 as a sensor of the intracellular redox state: contribution to cytoprotection mechanisms in oxidative stress 人类VDAC3作为细胞内氧化还原状态的传感器：在氧化应激中细胞保护机制的贡献

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-06-28 DOI: 10.1016/j.bbabio.2025.149565

Martyna Baranek-Grabińska , Tomasz Skrzypczak , Hanna Kmita , Andonis Karachitos

Voltage-dependent anion channels (VDACs) are essential for mitochondrial function, facilitating the exchange of metabolites between the cytosol and mitochondria. This study investigated the role of human VDAC paralogs, hVDAC1, hVDAC2, and hVDAC3, in maintaining mitochondrial function under oxidative stress in Saccharomyces cerevisiae strains lacking endogenous VDACs (encoded by POR1 and POR2) and antioxidant enzymes, i.e., superoxide dismutases (encoded by SOD1 and SOD2). The yeast cells expressing hVDAC3 showed stable growth under oxidative stress, maintained mitochondrial membrane potential and morphology, exhibited reduced superoxide anion levels, and achieved efficient ATP synthesis with minimal proton leak. In contrast, the cells expressing hVDAC1 or hVDAC2 presented impaired mitochondrial function which was supported by differences in bioenergetic profiles including ATP synthesis and proton leak but also FCCP uncoupling capacity and spare respiratory capacity. The cysteine-depleted variant of hVDAC3 (hVDAC3ΔCys) showed impaired cell growth under stress conditions, indicating that the cysteine residues in hVDAC3 are essential for its protective role. These findings highlight the unique protective function of hVDAC3 under oxidative stress, which is attributed to efficient metabolite transport and regulation via cysteine oxidation.

电压依赖性阴离子通道（vdac）对线粒体功能至关重要，促进细胞质和线粒体之间代谢物的交换。本研究研究了人类VDAC类似物hVDAC1、hVDAC2和hVDAC3在缺乏内源性VDAC（由POR1和POR2编码）和抗氧化酶，即超氧化物歧化酶（由SOD1和SOD2编码）的酿酒酵母菌株氧化应激下维持线粒体功能的作用。表达hVDAC3的酵母细胞在氧化应激下生长稳定，维持线粒体膜电位和形态，超氧阴离子水平降低，质子泄漏最小，ATP合成效率高。相反，表达hVDAC1或hVDAC2的细胞线粒体功能受损，这与生物能量谱的差异（包括ATP合成和质子泄漏）、FCCP解偶联能力和备用呼吸能力的差异有关。hVDAC3的半胱氨酸缺失变体（hVDAC3ΔCys）在应激条件下显示细胞生长受损，表明hVDAC3中的半胱氨酸残基对其保护作用至关重要。这些发现强调了hVDAC3在氧化应激下独特的保护功能，这归因于半胱氨酸氧化对代谢物的有效运输和调节。

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引用次数: 0

ATP requirements for growth reveal the bioenergetic impact of mitochondrial symbiosis 生长所需的ATP揭示了线粒体共生的生物能影响。

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics

Pub Date : 2025-06-23 DOI: 10.1016/j.bbabio.2025.149564

William F. Martin

Studies by microbiologists in the 1970s provided robust estimates for the energy supply and demand of a prokaryotic cell. The amount of ATP needed to support growth was calculated from the chemical composition of the cell and known enzymatic pathways that synthesize its constituents from known substrates in culture. Starting in 2015, geneticists and evolutionary biologists began investigating the bioenergetic role of mitochondria at eukaryote origin and energy in metazoan evolution using their own, widely trusted—but hitherto unvetted—model for the costs of growth in terms of ATP per cell. The more recent model contains, however, a severe and previously unrecognized error that systematically overestimates the ATP cost of amino acid synthesis up to 200-fold. The error applies to all organisms studied by such models and leads to conspicuously false inferences, for example that the synthesis of an average amino acid in humans requires 30 ATP, which no biochemistry textbook will confirm. Their ATP ‘cost’ calculations would require that E. coli obtains ~100 ATP per glucose and that mammals obtain ~240 ATP per glucose, untenable propositions that invalidate and void all evolutionary inferences so based. By contrast, established methods for estimating the ATP cost of microbial growth show that the first mitochondrial endosymbionts could have easily doubled the host's available ATP pool, provided (i) that genes for growth on environmental amino acids were transferred from the mitochondrial symbiont to the archaeal host, and (ii) that the host for mitochondrial origin was an autotroph using the acetyl-CoA pathway. Stated in simple terms, the significance of these findings are this: Life is a chemical reaction. It requires energy release in order to proceed. The currency of energy in cells is adenosine triphosphate, ATP. Five decades ago, microbiologists were able to measure and understand the amount of ATP that cells require to grow. New studies by evolutionary biologists have appeared in the meantime that brush aside the older microbiological findings, using their own methods to calculate the ATP cost of growth instead. Science is, however, an imperfect undertaking. The new studies contain a major error, similar to conflating centimeters with yards. The error affects many publications and their conclusions. Using the old methods, we can still meaningfully study the role of energy in evolution, including the origin of complex, nucleus-bearing cells.

微生物学家在20世纪70年代的研究为原核细胞的能量供应和需求提供了可靠的估计。支持生长所需ATP的数量是根据细胞的化学组成和已知的酶促途径来计算的，这些酶促途径是从已知的培养基中合成其成分的。从2015年开始，遗传学家和进化生物学家开始研究线粒体在真核生物起源中的生物能量作用，以及在后生动物进化中的能量，使用他们自己的、广泛信任的——但迄今为止尚未揭示的——以每个细胞ATP为单位的生长成本模型。然而，最近的模型包含了一个严重的、以前未被认识到的错误，即系统性地高估了氨基酸合成的ATP成本，最高可达200倍。这种错误适用于用这种模型研究的所有生物体，并导致明显错误的推论，例如，人类平均一个氨基酸的合成需要30个ATP，这是没有生物化学教科书可以证实的。他们的ATP“成本”计算要求大肠杆菌每葡萄糖获得约100个ATP，哺乳动物每葡萄糖获得约240个ATP，这是站不住脚的命题，使所有基于此的进化推断无效。相比之下，现有的估算微生物生长ATP成本的方法表明，第一个线粒体内共生体可以很容易地使宿主的可用ATP池翻倍，前提是：(i)在环境氨基酸上生长的基因从线粒体共生体转移到古菌宿主，（ii）线粒体起源的宿主是一个使用乙酰辅酶a途径的自养生物。意义声明：生命是一种化学反应。它需要能量释放才能进行。细胞中的能量货币是三磷酸腺苷ATP。50年前，微生物学家能够测量和了解细胞生长所需的ATP量。与此同时，进化生物学家的新研究也出现了，他们摒弃了以前的微生物学发现，转而使用自己的方法来计算生长所需的ATP成本。然而，科学是一项不完美的事业。新的研究包含一个重大错误，类似于将厘米与码混淆。这个错误影响了许多出版物和他们的结论。使用旧的方法，我们仍然可以有意义地研究能量在进化中的作用，包括复杂的有核细胞的起源。

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