A5056048979- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Metabolism and Genetic Disorders
- Microbial Metabolic Engineering and Bioproduction
- Genetics, Aging, and Longevity in Model Organisms
- Force Microscopy Techniques and Applications
- Photoreceptor and optogenetics research
- Cell Image Analysis Techniques
- Geological and Tectonic Studies in Latin America
- Advanced Electron Microscopy Techniques and Applications
- bioluminescence and chemiluminescence research
- Advanced biosensing and bioanalysis techniques
University of Bristol
2020-2024
MRC Mitochondrial Biology Unit
2017-2022
University of Cambridge
2018-2022
University of Freiburg
2022
Medical Research Council
2017-2018
The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as pore (PTP), inner membrane. Opening can be triggered by calcium ions, leading swelling organelle, disruption membrane, and ATP synthesis, followed cell death. Recent proposals suggest that is associated with synthase complex specifically ring c-subunits constitute membrane domain enzyme's rotor. c-subunit produced from three nuclear genes, ATP5G1, ATP5G2, ATP5G3, encoding identical...
The ATP synthase in human mitochondria is a membrane-bound assembly of 29 proteins 18 kinds. All but two membrane components are encoded nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the matrix organelle, where they assembled complex with ATP6 ATP8, products overlapping genes mitochondrial DNA. Disruption individual for nuclear-encoded subunits portion enzyme leads to formation intermediate vestigial ATPase complexes that provide description pathway domain. key...
Nearly all mitochondrial proteins need to be targeted for import from the cytosol. For majority, first port of call is translocase outer membrane (TOM complex), followed by a procession alternative molecular machines, conducting transport their final destination. The pre-sequence inner (TIM23-complex) imports with cleavable pre-sequences. Progress in understanding these mechanisms has been hampered poor sensitivity and time resolution assays. However, development an assay based on split...
Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric III; wherein subunit the former, NDUFA11, is conspicuously situated at interface. We identified nduf-11 (B0491.5) as encoding Caenorhabditis elegans homologue NDUFA11. Animals homozygous for CRISPR-Cas9-generated knockout allele arrested second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed to adulthood, enabling characterisation consequences:...
Mitochondrial ATP synthases form rows of dimers, which induce membrane curvature to give cristae their characteristic lamellar or tubular morphology. The angle formed between the central stalks synthase dimers varies species. Using cryo-electron tomography and sub-tomogram averaging, we determined structure dimer from nematode worm C. elegans show that differs previously structures. consequences this species-specific difference at interface were investigated by comparing S. cerevisiae...
Current methodologies for targeting the mitochondrial genome research and/or therapy development in diseases are restricted by practical limitations and technical inflexibility. A molecular toolbox CRISPR-mediated editing is desirable, as this could enable of mtDNA haplotypes using precision tuneability CRISPR enzymes. Such 'MitoCRISPR' systems described to date lack reproducibility independent corroboration. We have explored requirements MitoCRISPR human cells nuclease engineering,...
ABSTRACT Nearly all mitochondrial proteins need to be targeted for import from the cytosol. For majority, first port of call is translocase outer membrane (TOM complex), followed by a procession alternative molecular machines, conducting transport their final destination. The pre-sequence inner-membrane (TIM23-complex) imports with cleavable pre-sequences, and comes in two flavours: TIM23 SORT complex mediates inner (IMM) protein insertion MOTOR delivers matrix. Progress understanding these...
Abstract Mitochondrial ATP synthases form rows of dimers, which induce membrane curvature to give cristae their characteristic lamellar or tubular morphology. The angle formed between the central stalks synthase dimers varies species. Using cryo-electron tomography and sub-tomogram averaging, we determined structure dimer from nematode worm C. elegans show that differs previously structures. consequences this species-specific difference at interface were investigated by comparing S....
ABSTRACT Current methodologies for targeting the mitochondrial genome basic research and/or therapeutic strategy development in diseases are restricted by practical limitations and technical inflexibility. The of a functional molecular toolbox CRISPR-mediated editing is therefore desirable, as this could enable precise mtDNA haplotypes using precision tuneability CRISPR enzymes; however, published reports “MitoCRISPR” systems have, to date, lacked reproducibility independent corroboration....