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Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00071-9. doi: 10.1016/j.tibs.2024.03.005. Online ahead of print.ABSTRACTIn mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscop...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Scott A Jones Jonathan J Ruprecht Paul G Crichton Edmund R S Kunji Source Type: research

ULK/Atg1: phasing in and out of autophagy
Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00065-3. doi: 10.1016/j.tibs.2024.03.004. Online ahead of print.ABSTRACTAutophagy - a highly regulated intracellular degradation process - is pivotal in maintaining cellular homeostasis. Liquid-liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) fa...
Source: Trends in Biochemical Sciences - April 2, 2024 Category: Biochemistry Authors: Bo Wang Gautam Pareek Mondira Kundu Source Type: research

Limitations in membrane protein structure determination by lipid nanodiscs
Trends Biochem Sci. 2024 Mar 26:S0968-0004(24)00076-8. doi: 10.1016/j.tibs.2024.03.010. Online ahead of print.ABSTRACTLipid nanodiscs are popular mimetics of biological membranes for determining membrane protein structures. However, a recent study revealed that the choice of nanodisc scaffold directly influenced the structure of an ion channel. This finding prompts us to be cautious and calls for improved membrane mimetics for structure determination.PMID:38538407 | DOI:10.1016/j.tibs.2024.03.010 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - March 27, 2024 Category: Biochemistry Authors: Chen Zhao Source Type: research

Computationally guided AAV engineering for enhanced gene delivery
Trends Biochem Sci. 2024 Mar 25:S0968-0004(24)00054-9. doi: 10.1016/j.tibs.2024.03.002. Online ahead of print.ABSTRACTGene delivery vehicles based on adeno-associated viruses (AAVs) are enabling increasing success in human clinical trials, and they offer the promise of treating a broad spectrum of both genetic and non-genetic disorders. However, delivery efficiency and targeting must be improved to enable safe and effective therapies. In recent years, considerable effort has been invested in creating AAV variants with improved delivery, and computational approaches have been increasingly harnessed for AAV engineering. In t...
Source: Trends in Biochemical Sciences - March 26, 2024 Category: Biochemistry Authors: Jingxuan Guo Li F Lin Sydney V Oraskovich Julio A Rivera de Jes ús Jennifer Listgarten David V Schaffer Source Type: research

Dilation of ion selectivity filters in cation channels
Trends Biochem Sci. 2024 Mar 20:S0968-0004(24)00049-5. doi: 10.1016/j.tibs.2024.02.004. Online ahead of print.ABSTRACTIon channels establish the voltage gradient across cellular membranes by providing aqueous pathways for ions to selectively diffuse down their concentration gradients. The selectivity of any given channel for its favored ions has conventionally been viewed as a stable property, and in many cation channels, it is determined by an ion-selectivity filter within the external end of the ion-permeation pathway. In several instances, including voltage-activated K+ (Kv) channels, ATP-activated P2X receptor channels...
Source: Trends in Biochemical Sciences - March 21, 2024 Category: Biochemistry Authors: Kate Huffer Xiao-Feng Tan Ana I Fern ández-Mariño Surbhi Dhingra Kenton J Swartz Source Type: research

Macromolecular crowding sensing during osmotic stress in plants
Trends Biochem Sci. 2024 Mar 20:S0968-0004(24)00038-0. doi: 10.1016/j.tibs.2024.02.002. Online ahead of print.ABSTRACTOsmotic stress conditions occur at multiple stages of plant life. Changes in water availability caused by osmotic stress induce alterations in the mechanical properties of the plasma membrane, its interaction with the cell wall, and the concentration of macromolecules in the cytoplasm. We summarize the reported players involved in the sensing mechanisms of osmotic stress in plants. We discuss how changes in macromolecular crowding are perceived intracellularly by intrinsically disordered regions (IDRs) in p...
Source: Trends in Biochemical Sciences - March 21, 2024 Category: Biochemistry Authors: G I Meneses-Reyes D L Rodriguez-Bustos C L Cuevas-Velazquez Source Type: research

Promoting a MOSAIC future in science
Trends Biochem Sci. 2024 Mar 20:S0968-0004(24)00053-7. doi: 10.1016/j.tibs.2024.03.001. Online ahead of print.ABSTRACTDiscoveries at the frontiers of science and finding solutions to pressing biomedical problems will be accelerated when talent, which is widely distributed, is better aligned with opportunities. Strategies to enhance a MOSAIC (Maximizing Opportunities for Scientific and Academic Independent Careers) professoriate and diversify the biomedical landscape are discussed.PMID:38514275 | DOI:10.1016/j.tibs.2024.03.001 (Source: Trends in Biochemical Sciences)
Source: Trends in Biochemical Sciences - March 21, 2024 Category: Biochemistry Authors: Ruma Banerjee Kirsten F Block Source Type: research