Role of Mitochondria in Neuronal Apoptosis

Apoptosis is a controlled form of cell death that participates in the demise of neuronal cells during development, neurodegenerative disorders and exposure to neurotoxic agents. In recent years, the mitochondria have emerged as being pivotal in controlling apoptosis. They house a number of apoptogenic molecules that are released into the cytoplasm at the onset of apoptosis. These include cytochrome c, apoptosis-inducing factor and various caspases. Mitochondria also play an important role in intracellular Ca2+ regulation, which is crucial to excitotoxic neurodegeneration. Alterations in energy (ATP) production by mitochondria (due to hypoxia or mutations in genes encoding mitochondrial proteins of the electron transport chain) can induce apoptosis in neurons or increase their sensitivity to apoptosis.

• Publication year

  2000

• Venue

  Developmental Neuroscience

• Publication date

  2000-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1159/000017460PMID 11111150
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Calcineurin

  2007cited by this paper
• [Mitochondria and apoptosis].

  2000cited by this paper
• Cytochrome c release and caspase‐3 activation during colchicine‐induced apoptosis of cerebellar granule cells

  1999cited by this paper
• Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death.

  1999cited by this paper
• Apoptosis: Cell death defined by caspase activation

  1999cited by this paper
• Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia.

  1999cited by this paper
• Mitochondrial permeability transition induced DNA-fragmentation in the rat hippocampus following hypoglycemia.

  1999cited by this paper
• Cytochrome c and dATP-mediated Oligomerization of Apaf-1 Is a Prerequisite for Procaspase-9 Activation*

  1999cited by this paper
• Regulation of Apoptotic Protease Activating Factor-1 Oligomerization and Apoptosis by the WD-40 Repeat Region*

  1999cited by this paper
• BCL-2 family members and the mitochondria in apoptosis.

  1999cited by this paper
• Molecular characterization of mitochondrial apoptosis-inducing factor

  1999cited by this paper
• The Release of Cytochrome c from Mitochondria during Apoptosis of NGF-deprived Sympathetic Neurons Is a Reversible Event

  1999cited by this paper
• Caspases: their intracellular localization and translocation during apoptosis

  1999cited by this paper
• Implication of calpain in caspase activation during B cell clonal deletion

  1999cited by this paper
• Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process

  1999cited by this paper
• Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship.

  1999cited by this paper
• Presence of a pre‐apoptotic complex of pro‐caspase‐3, Hsp60 and Hsp10 in the mitochondrial fraction of Jurkat cells

  1999cited by this paper
• Ordering the Cytochrome c–initiated Caspase Cascade: Hierarchical Activation of Caspases-2, -3, -6, -7, -8, and -10 in a Caspase-9–dependent Manner

  1999cited by this paper
• Mitochondria in Neurodegeneration: Acute Ischemia and Chronic Neurodegenerative Diseases

  1999cited by this paper
• Hsp60 accelerates the maturation of pro‐caspase‐3 by upstream activator proteases during apoptosis

  1999cited by this paper
• Bid-induced Conformational Change of Bax Is Responsible for Mitochondrial Cytochrome c Release during Apoptosis

  1999cited by this paper
• Glutamate Neurotoxicity in Rat Cerebellar Granule Cells Involves Cytochrome c Release from Mitochondria and Mitochondrial Shuttle Impairment

  1999cited by this paper
• Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC

  1999cited by this paper
• Cyclosporine neurotoxicity: a review

  1999cited by this paper
• Apoptosis in neuronal cells: role of caspases.

  1998cited by this paper
• Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development.

  1998cited by this paper
• Bax directly induces release of cytochrome c from isolated mitochondria.

  1998cited by this paper
• Apoptotic Pathways: The Roads to Ruin

  1998cited by this paper
• Mitochondria - the Kraken wakes!

  1998cited by this paper
• Injected cytochrome c induces apoptosis

  1998cited by this paper
• Potassium Deprivation-Induced Apoptosis of Cerebellar Granule Neurons: Cytochrome c Release in the Absence of Altered Expression of Bcl-2 Family Proteins

  1998cited by this paper
• Oxidative Stress Induces a Form of Programmed Cell Death with Characteristics of Both Apoptosis and Necrosis in Neuronal Cells

  1998cited by this paper
• Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis.

  1998cited by this paper
• Cyclosporin A, But Not FK 506, Protects Mitochondria and Neurons against Hypoglycemic Damage and Implicates the Mitochondrial Permeability Transition in Cell Death

  1998cited by this paper
• The mitochondrial death/life regulator in apoptosis and necrosis.

  1998cited by this paper
• Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD‐specific caspase activation and independently of mitochondrial transmembrane depolarization

  1998cited by this paper
• Mitochondria and apoptosis.

  1998cited by this paper
• Neurotrophins: the biological paradox of survival factors eliciting apoptosis

  1998cited by this paper
• Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is inhibited by Bcl-2

  1998cited by this paper
• Relation of impaired energy metabolism to apoptosis and necrosis following transient cerebral hypoxia-ischaemia

  1998cited by this paper
• Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition

  1998cited by this paper
• Amelioration by cyclosporin A of brain damage in transient forebrain ischemia in the rat.

  1998cited by this paper
• Hypoxia induces apoptosis in human neuroblastoma SK‐N‐MC cells by caspase activation accompanying cytochrome c release from mitochondria

  1998cited by this paper
• Detection of pro‐caspase‐3 in cytosol and mitochondria of various tissues

  1998cited by this paper
• Evidence of a novel event during neuronal death: development of competence-to-die in response to cytoplasmic cytochrome c.

  1998cited by this paper
• Glutamate-induced neuron death requires mitochondrial calcium uptake

  1998cited by this paper
• The Caspase-3 Precursor Has a Cytosolic and Mitochondrial Distribution: Implications for Apoptotic Signaling

  1998cited by this paper
• Death by a thousand cuts: an ever increasing list of caspase substrates

  1998cited by this paper
• Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9.

  1998cited by this paper
• Apoptotic pathways: the roads to ruin.

  1998cited by this paper
• Blocking Cytochrome c Activity within Intact Neurons Inhibits Apoptosis

  1998cited by this paper
• Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria.

  1998cited by this paper
• Apaf1 is required for mitochondrial pathways of apoptosis and brain development.

  1998cited by this paper
• Cathepsin B-mediated activation of the proinflammatory caspase-11.

  1998cited by this paper
• Bcl-2 family proteins as ion-channels

  1998cited by this paper
• Differential requirement for caspase 9 in apoptotic pathways in vivo.

  1998cited by this paper
• Superoxide in Apoptosis

  1998cited by this paper
• CDK-independent activation of estrogen receptor by cyclin D1.

  1997cited by this paper
• Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis.

  1997cited by this paper
• Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease.

  1997cited by this paper
• Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis

  1997cited by this paper
• Bcl-xL forms an ion channel in synthetic lipid membranes

  1997cited by this paper
• Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c

  1997cited by this paper
• Termination of mammalian rDNA replication: polar arrest of replication fork movement by transcription termination factor TTF-I.

  1997cited by this paper
• Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons.

  1997cited by this paper
• Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.

  1997cited by this paper
• Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria.

  1997cited by this paper
• The MHC reactivity of the T cell repertoire prior to positive and negative selection.

  1997cited by this paper
• Energy supply and the shape of death in neurons and lymphoid cells

  1997cited by this paper
• Programmed cell death in neurons: focus on the pathway of nerve growth factor deprivation-induced death of sympathetic neurons.

  1997cited by this paper
• Alzheimer’s Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid β-Peptide: Involvement of Calcium and Oxyradicals

  1997cited by this paper
• Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.

  1997cited by this paper
• Cytochrome c: can't live with it--can't live without it.

  1997cited by this paper
• Mitochondrial Permeability Transition in the Central Nervous System: Induction by Calcium Cycling‐Dependent and ‐Independent Pathways

  1997cited by this paper
• Mitochondria accumulate Ca2+ following intense glutamate stimulation of cultured rat forebrain neurones.

  1997cited by this paper
• Amelioration by cyclosporin A of brain damage following 5 or 10 min of ischemia in rats subjected to preischemic hyperglycemia.

  1997cited by this paper
• Apoptosis and necrosis: Intracellular ATP level as a determinant for cell death modes

  1997cited by this paper
• Caspases: killer proteases.

  1997cited by this paper
• Release of apoptogenic proteins from the mitochondrial intermembrane space during the mitochondrial permeability transition

  1997cited by this paper
• Involvement of a Caspase‐3‐Like Cysteine Protease in 1‐Methyl‐4‐Phenylpyridinium‐Mediated Apoptosis of Cultured Cerebellar Granule Neurons

  1997cited by this paper
• Role of peroxide and superoxide anion during tumour cell apoptosis

  1997cited by this paper
• Understanding Parkinson's disease.

  1997cited by this paper
• Oxidative stress and apoptosis in neurodegeneration.

  1996cited by this paper
• Mitochondrial Dysfunction Is a Primary Event in Glutamate Neurotoxicity

  1996cited by this paper
• Mitochondrial Depolarization in Glutamate-Stimulated Neurons: An Early Signal Specific to Excitotoxin Exposure

  1996cited by this paper
• Programmed cell death in the developing nervous system.

  1996cited by this paper
• Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation

  1996cited by this paper
• 1,10-Phenanthroline stimulates internucleosomal DNA fragmentation in isolated rat-liver nuclei by promoting the redox activity of endogenous copper ions.

  1996cited by this paper
• Mitochondria, Calcium Regulation, and Acute Glutamate Excitotoxicity in Cultured Cerebellar Granule Cells

  1996cited by this paper
• Programmed Cell Death in the Developing Nervous System

  1996cited by this paper
• Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice

  1996cited by this paper
• Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes.

  1996cited by this paper
• The death domain: a module shared by proteins with diverse cellular functions.

  1995cited by this paper
• The mitochondrial permeability transition.

  1995cited by this paper
• Apoptosis in the developing CNS.

  1995cited by this paper
• Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function.

  1995cited by this paper
• Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL

  1995cited by this paper
• Colchicine induces apoptosis in cerebellar granule cells.

  1995cited by this paper
• Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis

  1995cited by this paper
• Are reactive oxygen species involved in Alzheimer's disease?

  1995cited by this paper

• Mitochondrial Quality Control: Insights into Intracerebral Hemorrhage

  2025cites this paper
• Microglia energy metabolism: A new perspective on Alzheimer's disease treatment.

  2025cites this paper
• The Effect of Psoralea corylifolia (Babchi) on Neuronal Apoptosis Induced by Palmitate in PC12 Cells and its Role in Alzheimer’s Disease: A Review

  2024cites this paper
• Ca2+-Permeable TRPV1 Receptor Mediates Neuroprotective Effects in a Mouse Model of Alzheimer’s Disease via BDNF/CREB Signaling Pathway

  2023cites this paper
• Neuroprotective effect of Deodeok (Codonopsis lanceolata) bud extracts in H2O2-stimulated SH-SY5Y cells

  2023cites this paper
• A mechanistic overview of spinal cord injury, oxidative DNA damage repair and neuroprotective therapies

  2021cites this paper
• Cannabinoids and mitochondria

  2021cites this paper
• Fas apoptotic inhibitory molecule 2: a novel regulator of autophagy by facilitating autophagosome-lysosome fusion

  2020cites this paper
• Sevoflurane increases intracellular calcium to induce mitochondrial injury and neuroapoptosis.

  2020cites this paper
• Corticotropin-releasing hormone (CRH) alters mitochondrial morphology and function by activating the NF-kB-DRP1 axis in hippocampal neurons

  2020cites this paper
• Adenosine and Its Receptors as Potential Drug Targets in Amyotrophic Lateral Sclerosis

  2019cites this paper
• Regulatory role of calpain in neuronal death

  2018cites this paper
• Pathological Impacts of Chronic Hypoxia on Alzheimer's Disease.

  2018cites this paper
• [Metabonomics studies of urine from APP/PS1 mice with early-stage Alzheimer's disease].

  2018cites this paper
• Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

  2017cites this paper
• Insight into potential mechanisms of hypobaric hypoxia–induced learning and memory deficit – Lessons from rat studies

  2017cites this paper
• Neuroprotective effects of the Phellinus linteus ethyl acetate extract against H2O2-induced apoptotic cell death of SK-N-MC cells.

  2016cites this paper
• Formulating multicellular models of metabolism in tissues : application to energy metabolism in the human brain

  2016cites this paper
• Control of adult neurogenesis by programmed cell death in the mammalian brain

  2016cites this paper
• Autophagy for the quality control of adult hippocampal neural stem cells.

  2016cites this paper
• Beneficial Effect of Flavone Derivatives on Aβ-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α

  2015cites this paper
• Therapeutic strategies in Parkinson's disease: what we have learned from animal models

  2015cites this paper
• Amide-type adduct of dopamine - plausible cause of Parkinson diseases.

  2014cites this paper
• Neuroprotective effects of corn silk maysin via inhibition of H2O2-induced apoptotic cell death in SK-N-MC cells.

  2014cites this paper
• Applications of proteomics in cartilage biology and osteoarthritis research.

  2011cites this paper
• A possible pivotal role of mitochondrial free calcium in neurotoxicity mediated by N-methyl-d-aspartate receptors in cultured rat hippocampal neurons.

  2011cites this paper
• Aging and Apoptosis in Muscle

  2011cites this paper
• Mechanism of pyrethroid pesticide-induced apoptosis: role of calpain and the ER stress pathway.

  2011cites this paper
• Nuclear Apoptosis and Sarcopenia

  2011cites this paper
• Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson's disease.

  2011cites this paper
• Large-scale in silico modeling of metabolic interactions between cell types in the human brain

  2010cites this paper
• Overexpression of Tau Proteins Antagonizes Amyloid-β-Potentiated Apoptosis Through Mitochondria-Caspase-3 Pathway in N2a Cells

  2010cites this paper
• Region-specific protein abundance changes in the brain of MPTP-induced Parkinson's disease mouse model.

  2010cites this paper
• Interaction of neurotrophin signaling with Bcl‐2 localized to the mitochondria and endoplasmic reticulum on spiral ganglion neuron survival and neurite growth

  2010cites this paper
• Environmental toxins and Parkinson’s disease: Putative roles of impaired electron transport chain and oxidative stress

  2010cites this paper
• Vekstfaktorers interaksjoner med caspaser i PC12-cellelinjen og kornceller fra rotte

  2009cites this paper
• PCB i miljøet som mulig årsak til utvikling av ADHD : Målinger av reseptorbinding og aminosyrenivå i hjernen

  2009cites this paper
• Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: Complementary roles of L-type calcium channel and NMDA receptors.

  2009cites this paper
• Response and adaptation of skeletal muscle to denervation stress: the role of apoptosis in muscle loss.

  2009cites this paper
• Opposing roles of prion protein in oxidative stress- and ER stress-induced apoptotic signaling.

  2008cites this paper
• Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats.

  2008cites this paper
• Formation of Dopamine Adducts Derived from Brain Polyunsaturated Fatty Acids

  2008cites this paper
• Neuropathology in Drosophila Mutants With Increased Seizure Susceptibility

  2008cites this paper
• Hypoxia affects the physiological behavior of rat cortical synaptosomes.

  2007cites this paper
• Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord injury.

  2007cites this paper
• Cysteine-Mediated Excitotoxic Neuronal Death is an Apoptosis—Necrosis Continuum

  2007cites this paper
• Caspase-9 regulates apoptosis/proliferation balance during metamorphic brain remodeling in Xenopus

  2007cites this paper
• Alzheimer's Disease: A Complex Paradigm

  2007cites this paper
• Mechanisms and modulation of neural cell damage induced by oxidative stress.

  2007cites this paper
• Mitochondrial electron transport in models of neuropathic and inflammatory pain

  2006cites this paper
• Functional analysis of the apoptosis-inducing factor (AIF)

  2006cites this paper
• Structure-function Analysis of NRAGE : A Protein Involved in Developmental Neural Apoptosis

  2006cites this paper
• Malonate induces cell death via mitochondrial potential collapse and delayed swelling through an ROS‐dependent pathway

  2005cites this paper
• Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors.

  2005cites this paper
• Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture.

  2005cites this paper
• Neuroprotective mechanisms of curcumin against cerebral ischemia‐induced neuronal apoptosis and behavioral deficits

  2005cites this paper
• Diferenciación sexual en el sistema nervioso central Sexual differentiation in the central nervous system

  2005cites this paper
• The Effect of Mild and Severe Hypoxia on Rat Cortical Synaptosomes

  2005cites this paper
• Glutamate mediates cell death and increases the Bax to Bcl-2 ratio in a differentiated neuronal cell line.

  2004cites this paper
• Angiotensin II attenuates NMDA receptor-mediated neuronal cell death and prevents the associated reduction in Bcl-2 expression.

  2004cites this paper
• Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications

  2004cites this paper
• AATF protects neural cells against oxidative damage induced by amyloid beta-peptide.

  2004cites this paper
• Apoptotic adaptations from exercise training in skeletal and cardiac muscles

  2004cites this paper
• Involvement of increased stability of mitochondrial membrane potential and overexpression of Bcl-2 in enhanced anoxic tolerance induced by hypoxic preconditioning in cultured hypothalamic neurons.

  2004cites this paper
• Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria.

  2004cites this paper
• Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2.

  2004cites this paper
• Estudio funcional y molecular del canal Maxi-Cl activado por antiestrógenos

  2004cites this paper
• Dynamic analysis of apoptosis in primary cortical neurons by fixed- and real-time cytofluorometry

  2004cites this paper
• Ischemia Leads to Apoptosis—and Necrosis‐like Neuron Death in the Ischemic Rat Hippocampus

  2004cites this paper
• Medicinal ChemistryApproaches for theTreatment and Prevention of Alzheimer's Disease

  2003cites this paper
• Involvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death

  2003cites this paper
• Inhibition of α‐ketoglutarate dehydrogenase complex promotes cytochrome c release from mitochondria, caspase‐3 activation, and necrotic cell death

  2003cites this paper
• The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders.

  2003cites this paper
• Effects of Hydrogen Sulfide on Neurobehavioral Function

  2003cites this paper
• Apoptosis vs Nonapoptotic Mechanisms in Neurodegeneration

  2003cites this paper
• The contributions of excitotoxicity, glutathione depletion and DNA repair in chemically induced injury to neurones: exemplified with toxic effects on cerebellar granule cells

  2003cites this paper
• Medicinal chemistry approaches for the treatment and prevention of Alzheimer's disease

  2003cites this paper
• Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress

  2003cites this paper
• Direct evidence for membrane pore formation by the apoptotic protein Bax.

  2002cites this paper
• Glucose/mitochondria in neurological conditions.

  2002cites this paper
• Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3

  2002cites this paper
• Cell death in adult neural stem cells

  2002cites this paper
• The effects of endocrine disrupting chemicals on the ovary.

  2002cites this paper
• NRAGE, a p75 Neurotrophin Receptor-interacting Protein, Induces Caspase Activation and Cell Death through a JNK-dependent Mitochondrial Pathway*

  2002cites this paper
• Activation of Mitochondrial ATP-Dependent Potassium Channels Protects Neurons against Ischemia-Induced Death by a Mechanism Involving Suppression of Bax Translocation and Cytochrome c Release

  2002cites this paper
• Embryo Toxicity and Teratogenicity of Formaldehyde

  2001cites this paper
• Ultrastructural characteristics of necrotic and apoptotic mode of neuronal cell death in a model of anoxia in vitro.

  2001cites this paper
• Bidirectional regulation of mitochondrial gene expression during developmental neuroplasticity of visual cortex.

  2001cites this paper
• Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death.

  2000cites this paper
• Annals of the New York Academy of Sciences Therapeutic Strategies in Parkinson's Disease: What We Have Learned from Animal Models

  year unknowncites this paper