The inner membrane of mitochondria is especially protein-rich. To direct proteins into the inner membrane, translocases mediate transport and membrane insertion of precursor proteins. Although the majority of mitochondrial proteins are imported from the cytoplasm, core subunits of respiratory chain complexes are inserted into the inner membrane from the matrix. Oxa1, a conserved membrane protein, mediates the insertion of mitochondrion-encoded precursors into the inner mitochondrial membrane. The molecular mechanism by which Oxa1 mediates insertion of membrane spans, entailing the translocation of hydrophilic domains across the inner membrane, is still unknown. We investigated if Oxa1 could act as a protein-conducting channel for precursor transport. Using a biophysical approach, we show that Oxa1 can form a pore capable of accommodating a translocating protein segment. After purification and reconstitution, Oxa1 acts as a cation-selective channel that specifically responds to mitochondrial export signals. The aqueous pore formed by Oxa1 displays highly dynamic characteristics with a restriction zone diameter between 0.6 and 2 nm, which would suffice for polypeptide translocation across the membrane. Single channel analyses revealed four discrete channels per active unit, suggesting that the Oxa1 complex forms several cooperative hydrophilic pores in the inner membrane. Hence, Oxa1 behaves as a pore-forming translocase that is regulated in a membrane potential and substrate-dependent manner.
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http://dx.doi.org/10.1074/jbc.M112.387563 | DOI Listing |
Int J Mol Sci
December 2024
Caruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033, USA.
Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy.
Cancer cells undergo remarkable metabolic changes to meet their high energetic and biosynthetic demands. The Warburg effect is the most well-characterized metabolic alteration, driving cancer cells to catabolize glucose through aerobic glycolysis to promote proliferation. Another prominent metabolic hallmark of cancer cells is their increased reliance on glutamine to replenish tricarboxylic acid (TCA) cycle intermediates essential for ATP production, aspartate and fatty acid synthesis, and maintaining redox homeostasis.
View Article and Find Full Text PDFOphthalmology
January 2025
University of Bordeaux, INSERM, BPH, U1219, F-33000 Bordeaux, France; FRCRnet, F-CRIN network, France.
Purpose: We assessed the associations of macular layer thicknesses, measured using spectral-domain OCT (SD-OCT), with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRS).
Design: Population-based cohort study PARTICIPANTS: 653 participants of the Alienor study, with biennial eye imaging from 2009 to 2024.
Methods: Macular layer thicknesses of eight distinct layers and three compound layers were automatically segmented based on SD-OCT imaging of the macula.
J Mater Chem B
January 2025
Department of Physics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Microlife
January 2025
Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), D-97080 Würzburg, Germany.
Bacterial small proteins impact diverse physiological processes, however, technical challenges posed by small size hampered their systematic identification and biochemical characterization. In our quest to uncover small proteins relevant for pathogenicity, we previously identified YjiS, a 54 amino acid protein, which is strongly induced during this pathogen's intracellular infection stage. Here, we set out to further characterize the role of YjiS.
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