Mitochondria metabolism sets the species-specific tempo of neuronal development

Science, Journal Year: 2023, Volume and Issue: 379(6632)

Published: Jan. 27, 2023

Neuronal development in the human cerebral cortex is considerably prolonged compared with that of other mammals. We explored whether mitochondria influence species-specific timing cortical neuron maturation. By comparing and mouse neuronal maturation at high temporal cell resolution, we found a slower neurons mouse, together lower metabolic activity, particularly oxidative phosphorylation. Stimulation metabolism resulted accelerated vitro vivo, leading to cells weeks ahead time, whereas its inhibition led decreased rates Mitochondria are thus important regulators pace underlying human-specific brain neoteny.

Language: Английский

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A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in cortical organoids

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111853 - 111853

Published: Jan. 21, 2025

Language: Английский

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Mitochondrial function in spinal cord injury and regeneration

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(5)

Published: April 13, 2022

Language: Английский

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Emerging evidence for astrocyte dysfunction in schizophrenia

Glia, Journal Year: 2022, Volume and Issue: 70(9), P. 1585 - 1604

Published: May 30, 2022

Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, precise etiology still poorly understood. not characterized by gross pathology, but involves subtle pathological changes in neuronal populations glial cells. Among the latter, astrocytes critically contribute to regulation of neurodevelopmental processes, any dysfunctions their morphological functional maturation may lead aberrant processes involved pathogenesis schizophrenia, such as mitochondrial biogenesis, synaptogenesis, glutamatergic dopaminergic transmission. Studies mechanisms regulating astrocyte therefore improve our understanding cellular molecular underlying schizophrenia.

Language: Английский

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Mitophagy: A promising therapeutic target for neuroprotection during ageing and age‐related diseases

British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 180(12), P. 1542 - 1561

Published: Feb. 16, 2023

Mitochondria and mitochondria-mediated signalling pathways are known to control synaptic signalling, as well long-lasting changes in neuronal structure function. Mitochondrial impairment is linked dysfunction normal ageing age-associated neurodegenerative ailments, including Parkinson's disease (PD) Alzheimer's (AD). Both proteolysis mitophagy perform a major role neuroprotection, by maintaining healthy mitochondrial population during ageing. Mitophagy, highly evolutionarily conserved cellular process, helps the clearance of damaged mitochondria thereby maintains metabolic balance, energy supply, survival health. Besides maintenance brain homeostasis, hippocampal also synapse formation, axonal development, dopamine release long-term depression. In contrast, defective contributes age-related neurodegeneration promoting accumulation leading dysfunction. Exercise, stress management, dynamics administering natural or synthetic pharmacological compounds some strategies used for neuroprotection neurological diseases. The current review discusses impact conditions, underlying molecular potential therapies based on recently elucidated mitophagy-inducing strategies.

Language: Английский

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Psychosocial experiences are associated with human brain mitochondrial biology

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(27)

Published: June 18, 2024

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position both as targets drivers psychosocial experiences. On one hand, chronic stress exposure mood states may alter multiple aspects mitochondrial biology; other functional variations in OxPhos capacity social behavior, reactivity, mood. But are exposures subjective linked to biology human brain? By combining longitudinal antemortem assessments factors with postmortem (dorsolateral prefrontal cortex) proteomics older adults, we find that higher well-being is greater abundance machinery, whereas negative lower protein content. Combined, positive explained 18 25% variance complex I, primary biochemical entry point energizes mitochondria. Moreover, interrogating psychobiological specific neuronal nonneuronal cells single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific for glia opposite neurons. As a result, “mind-mitochondria” were masked bulk RNA-seq, highlighting likely underestimation true effect sizes tissues. Thus, self-reported phenotypes.

Language: Английский

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Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 197, P. 106520 - 106520

Published: May 3, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental affecting 1 in 36 children and associated with physiological abnormalities, most notably mitochondrial dysfunction, at least subset of individuals. This systematic review meta-analysis discovered 204 relevant articles which evaluated biomarkers dysfunction ASD Significant elevations (all p < 0.01) the prevalence lactate (17%), pyruvate (41%), alanine (15%) creatine kinase (9%) were found ASD. Individuals had significant differences moderate to large effect sizes (Cohen's d' ≥ 0.6) compared controls mean pyruvate, lactate-to-pyruvate ratio, ATP, kinase. Some studies abnormal TCA cycle metabolites Thirteen controlled reported DNA (mtDNA) deletions or variations group blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, brain. Meta-analyses (p copy number mtDNA overall ND1, ND4 CytB genes. Four linked specific haplogroups A series subgroup elevated respiration was increased sensitivity mitochondria stressors regression. Lactate, carnitine, acyl-carnitines clinical features such as delays language, social interaction, cognition, motor skills, repetitive behaviors gastrointestinal symptoms, although not all an association. acyl-carnitines, CoQ10, well variants, heteroplasmy, severity. Variability across biomarker primarily due collection processing techniques intrinsic heterogeneity population. Several alterations metabolism mothers neonates who develop Treatments targeting mitochondria, particularly carnitine ubiquinol, appear beneficial The link between common abnormalities individuals including disorders, oxidative stress, immune outlined. subtypes are discussed, one related regression, another microbiome metabolites, acyl-carnitines. Mechanisms linking function prenatal brain development postnatal Given multisystem complexity some ASD, this presents evidence for being central by contributing development, comorbidities diagnostic approach identify From evidence, it clear that many have may need be addressed order achieve optimal outcomes. fact during pregnancy early life eventually provides promise predictive Further improve understanding role better defining subgroups molecular mechanisms driving unique changes those

Language: Английский

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Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 4, 2024

Abstract Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during development and maintenance. During embryonic adult neurogenesis, NSCs undergo metabolic switch from glycolytic to oxidative phosphorylation with rise mitochondrial DNA (mtDNA) content, changes mitochondria shape size, physiological augmentation reactive oxygen species which together drive proliferate differentiate. Genetic epigenetic modifications proteins involved cellular differentiation (Mechanistic Target Rapamycin), proliferation (Wingless-type), hypoxia (Mitogen-activated protein kinase)–and all connected by common key regulatory factor Hypoxia Inducible Factor-1A–are deemed be responsible for shift and, consequently, NSC pathological conditions. Both primary dysfunction due mutations nuclear or mtDNA secondary (OXPHOS) metabolism, dynamics, organelle interplay pathways can contribute neurodevelopmental progressive neurodegenerative disorders. This review analyses physiology pathology starting available vitro vivo models highlights current knowledge concerning this process.

Language: Английский

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Metabolic mechanisms of species-specific developmental tempo

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(13), P. 1628 - 1639

Published: June 20, 2024

Development consists of a highly ordered suite steps and transitions, like choreography. Although these sequences are often evolutionarily conserved, they can display species variations in duration speed, thereby modifying final organ size or function. Despite their evolutionary significance, the mechanisms underlying species-specific scaling developmental tempo have remained unclear. Here, we will review recent findings that implicate global cellular mechanisms, particularly intermediary protein metabolism, as modifiers tempo. In various systems, from somitic cell oscillations to neuronal development, metabolic pathways differences. These been linked mitochondrial which influence speed transitions. Thus, regulate together with other processes, including proteostasis chromatin remodeling. By linking metabolism evolution trajectories, provide opportunities decipher how timing organism fitness.

Language: Английский

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Cellular and Molecular Mechanisms Linking Human Cortical Development and Evolution

Annual Review of Genetics, Journal Year: 2021, Volume and Issue: 55(1), P. 555 - 581

Published: Sept. 18, 2021

The cerebral cortex is at the core of brain functions that are thought to be particularly developed in human species. Human specificities stem from divergent features corticogenesis, leading increased cortical size and complexity. Underlying cellular mechanisms include prolonged patterns neuronal generation maturation, as well amplification specific types stem/progenitor cells. While gene regulatory networks corticogenesis appear largely conserved among all mammals including humans, they have evolved primates, species, through emergence rapidly transcriptional elements, recently duplicated novel genes. These human-specific molecular together control key milestones often affected neurodevelopmental disorders, thus linking neural development, evolution, diseases.

Language: Английский

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