Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Abstract In neurons of the mammalian central nervous system (CNS), axonal mitochondria are thought to be indispensable for supplying ATP during energy-consuming processes such as neurotransmitter release. Here, we demonstrate using multiple, independent, in vitro and vivo approaches that majority (∼80-90%) cortical pyramidal (CPNs), lack mitochondrial DNA (mtDNA). Using dynamic, optical imaging analysis genetically encoded sensors matrix pH, axons CPNs, but not their dendrites, complex V (ATP synthase) functions a reverse way, consuming protruding H + out maintain membrane potential. Our results do play major role supply, despite playing other critical regulating neurotransmission Ca 2+ buffering.

Language: Английский

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Neural differentiation in perspective: mitochondria as early programmers

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 8, 2025

Neural differentiation during development of the nervous system has been extensively studied for decades. These efforts have culminated in generation a detailed map developmental events that appear to be associated with emergence committed cells system. In this review landscape neural is revisited by focusing on abiotic signals play role induction differentiation. Evidence presented regarding chimeric whereby generated mitochondria orchestrate early This stage, characterised mitochondrial hyperactivity, turn triggers late stage reprogramming activity biotic signals.

Language: Английский

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Tapping natures rhythm: the role of season in mitochondrial function and genetics in the UK biobank

Human Genomics, Journal Year: 2025, Volume and Issue: 19(1)

Published: March 29, 2025

Abstract Background Mitochondria are small organelles inside our cells crucial for producing energy and heat, cell signaling, production degradation of important molecules, as well death. The number mitochondria in each is a marker mitochondrial function, which generally declines with increasing age. However, we found that there also considerable seasonal variation abundance, warrants further research. Methods We leveraged data from individuals participating the UK Biobank study computed their abundance Exome sequencing reads mapping to genome. effect was modelled sine-cosine function across year changes amplitude, acrophase displacement due various demographic, lifestyle, genetic, proteomic, metabolomic markers were investigated multivariate regression. Results DNA (mtDNA) higher winter than summer. This difference related advanced age, BMI smoking behavior resulted reduced amplitude mtDNA abundance. A education (i.e., shifted distribution earlier year) lack physical activity led later acrophase. Generally, increased immune count lower an platelet lymphocyte increase Importantly, associated risk cardiovascular, digestive, genitourinary, respiratory diseases all-cause mortality. Most proteomic baseline level) but not or amplitude. Similarly, multiple genetic variants influencing displacement, none reached genome-wide significance when investigating Conclusion Seasonal influenced by environmental, lifestyle parameters. Differences oscillation could potentially explain discrepancies previous associations results might be useful improve future prediction.

Language: Английский

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The alternative oxidase reconfigures the larval mitochondrial electron transport system to accelerate growth and development in Drosophila melanogaster

Published: May 9, 2025

Abstract The alternative oxidase (AOX) is naturally present in the mitochondrial electron transfer system (ETS) of many organisms but absent vertebrates and most insects. AOX oxidizes coenzyme Q reduces O2 H2O, partially replacing ETS cytochrome c segment alleviating oxidative stress caused by overload. As successfully demonstrated animal models, shows potential mitigating diseases. However, its non-proton-pumping nature may uncouple mitochondria, leading to excessive heat generation interference with normal metabolism physiology. Here we show that from tunicate Ciona intestinalis accelerates development Drosophila melanogaster, elevating larval biomass accumulation (primarily due increased fat), mobility food intake, without increasing body production. intensifies Leak respiration lowers phosphorylation efficiency through functional interactions glycerol-3-phosphate dehydrogenase (mGPDH). This associated complex I (CI)-driven supercomplex formation, higher cellular NAD+/NADH ratios, an enhanced flux central carbon metabolism. Chemical uncouplers rotenone confirm roles uncoupling CI AOX-expressing larvae. Thus, appears be promoting growth reinforcing proliferative metabolic program via intricate mechanism reconfigures ETS.

Language: Английский

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The alternative oxidase reconfigures the larval mitochondrial electron transport system to accelerate growth and development in Drosophila melanogaster

Published: May 9, 2025

Abstract The alternative oxidase (AOX) is naturally present in the mitochondrial electron transfer system (ETS) of many organisms but absent vertebrates and most insects. AOX oxidizes coenzyme Q reduces O2 H2O, partially replacing ETS cytochrome c segment alleviating oxidative stress caused by overload. As successfully demonstrated animal models, shows potential mitigating diseases. However, its non-proton-pumping nature may uncouple mitochondria, leading to excessive heat generation interference with normal metabolism physiology. Here we show that from tunicate Ciona intestinalis accelerates development Drosophila melanogaster, elevating larval biomass accumulation (primarily due increased fat), mobility food intake, without increasing body production. intensifies Leak respiration lowers phosphorylation efficiency through functional interactions glycerol-3-phosphate dehydrogenase (mGPDH). This associated complex I (CI)-driven supercomplex formation, higher cellular NAD+/NADH ratios, an enhanced flux central carbon metabolism. Chemical uncouplers rotenone confirm roles uncoupling CI AOX-expressing larvae. Thus, appears be promoting growth reinforcing proliferative metabolic program via intricate mechanism reconfigures ETS.

Language: Английский

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Most Axonal Mitochondria in Cortical Pyramidal Neurons Lack Mitochondrial DNA and Consume ATP

Published: Jan. 1, 2024

Language: Английский

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Mitochondrial Thermogenesis Can Trigger Heat Shock Response in the Nucleus

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(6), P. 1231 - 1241

Published: June 3, 2024

Mitochondrial thermogenesis is a process in which heat generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively fat cells with little knowledge on how may act beyond energy expenditure. Here, we highlight exothermic oxygen reduction reaction (ΔHf° = −286 kJ/mol) main source of protonophore-induced thermogenesis, and this conducted to other cellular organelles, including nucleus. As result, reached nucleus initiated classical shock response, formation nuclear stress granules localization factor 1 (HSF1) chromatin. Consequently, activated HSF1 increases level gene expression associated response thermal mammalian cells. Our results illustrate within as potential mitochondria-nucleus communication expand our understanding biological functions mitochondria cell physiology.

Language: Английский

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Temperature-sensing riboceptors

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 1 - 6

Published: July 17, 2024

Understanding how cells sense temperature is a fundamental question in biology and pivotal for the evolution of life. In numerous organisms, not only sensed but also generated due to cellular processes. Consequently, mechanisms governing sensation various organisms have been experimentally elucidated. Extending upon others' proposals demonstration protein- nucleic acid-based thermosensors, utilizing colonial India 'punkah-wallahs' analogy, I present my rationale necessity sensing every organelle cell. Finally, propose temperature-sensing riboceptors (ribonucleic acid receptors) integrate all RNA molecules (mRNA, non-coding RNA, so forth) capable triggering signaling event, which call as thermocrine signaling. This approach could enable identification cell almost organism, other classes ligands, including gaseous solutes, water.

Language: Английский

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The protein‐only RNase Ps, endonucleases that cleave pre‐tRNA: Biological relevance, molecular architectures, substrate recognition and specificity, and protein interactomes

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(2)

Published: March 1, 2024

Abstract Protein‐only RNase P (PRORP) is an essential enzyme responsible for the 5′ maturation of precursor tRNAs (pre‐tRNAs). PRORPs are classified into three categories with unique molecular architectures, although all classes share a mechanism and have similar active sites. Single subunit PRORPs, like those found in plants, multiple isoforms different localizations, substrate specificities, temperature sensitivities. Most recently, Arabidopsis thaliana PRORP2 was shown to interact TRM1A B, highlighting new potential role between these enzymes. Work At led development ribonuclease that being used protect against plant viruses. The mitochondrial complex, metazoans, consists PRORP, TRMT10C, SDR5C1, has also been specificity, cause unknown. Mutations tRNA linked human disease, need continue understanding this complex. last class homologs Aquifex (HARPs), thermophilic archaea bacteria. This most recently discovered type PRORP forms large homo‐oligomer Although numerous structures HARPs published, it still unclear how bind pre‐tRNAs what ratio. There little investigation specificity ideal conditions HARPs. Moving forward, further work required fully characterize each pre‐tRNA binding recognition mechanism, rules distinct evolved. article categorized under: RNA Structure Dynamics > Structure, Chemistry Influence Biological Systems

Language: Английский

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Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1141 - 1141

Published: July 3, 2024

Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed master regulator of UPR, IRE1 (inositol-requiring enzyme 1) protein, is clustered as result UPR activation human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, temperature-sensitive fluorescent probe targeted to endoplasmic reticulum (ER), we detected significant intracellular thermogenesis mouse embryonic fibroblast (MEF) Temperatures reached at least 8 °C higher than external environment (40 °C), resulting exceptionally high temperatures similar those previously described for mitochondria. Mild heat-induced MEF cells was likely due uncoupling Ca2+/ATPase (SERCA) pump. The initiated pronounced cytosolic heat-shock cells, which significantly lower U2OS both and SERCA pump were absent. results suggest depending on intrinsic cellular properties, hyperthermia-induced defines mechanism determines outcome hyperthermic

Language: Английский

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