ReviewCell research2018
m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.
Review in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Mitochondrial Proteomes in Neural Cells: A Systematic Review.Biomolecules · 2023Pooled it
- A selective inhibitor reveals roles for LONP1 in mitochondrial proteostasis and OXPHOS dependencies.Life science alliance · 2026Article
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- Structural basis for prohibitin-mediated regulation of mitochondrial m-AAA protease.Nature communications · 2026Article
- VPS13A Deficiency Leads to Impaired Lipid Distribution and Alteration of Mitochondrial Calcium Homeostasis in Fibroblasts of VPS13A Disease Patients.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- Blockade of Presynaptic αNeurochemical research · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Membrane-embedded polar residues target membrane proteins for degradation by the quality control protease FtsH.Nature communications · 2026Article
- Molecular characterization of recessively inherited ataxic and neuropathic disorders in consanguineous Pakistani families.Scientific reports · 2026Article
- Physalin F Promotes AFG3L2-Mediated Degradation of VISA/MAVS to Suppress Innate Immune Response to RNA Virus.Pathogens (Basel, Switzerland) · 2026Article
- Editorial: Proteostasis disruption in neurodegenerative disorders: mechanisms and treatment strategies.Frontiers in molecular neuroscience · 2026Article
- MCU knockdown attenuates cisplatin-induced damage of auditory cells: potential involvement of PI3K/AKT/mTOR signaling and autophagy-related processes.Frontiers in pharmacology · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- SLC25A39 overexpression exacerbates lung adenocarcinoma progression and is negatively regulated by AFG3L2.NPJ precision oncology · 2025Article
- Biallelic Variants in AFG3L2 Causing Spastic Ataxia Type 5 (SPAX5): Report of Two Pediatric Cases from Bogotá, Colombia.Movement disorders clinical practice · 2025Article
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Mitochondrial Quality Control in Health and Disease.MedComm · 2025Review
- Mitochondrial calcium signaling regulates branched-chain amino acid catabolism in fibrolamellar carcinoma.Science advances · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.