The machineries, regulation and cellular functions of mitochondrial calcium
Open accessAbstract
Calcium ions (Ca 2+) are some of the most versatile signalling molecules, and they have many physiological functions, prominently including muscle contraction, neuronal excitability, cell migration and cell growth. By sequestering and releasing Ca 2+, mitochondria serve as important regulators of cellular Ca 2+. Mitochondrial Ca 2+ also has other important functions, such as regulation of mitochondrial metabolism, ATP production and cell death. In recent years, identification of the molecular machinery regulating mitochondrial Ca 2+ accumulation and efflux has expanded the number of (patho)physiological conditions that rely on mitochondrial Ca 2+ homeostasis. Thus, expanding the understanding of the mechanisms of mitochondrial Ca 2+ regulation and function in different cell types is an important task in biomedical research, which offers the possibility of targeting mitochondrial Ca 2+ machinery for the treatment of several disorders.
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Mitochondria are involved in neuronal redox homeostasis, reactive oxygen species production, calcium buffering, and intracellular signaling.
“Mitochondria are also involved in neuronal redox homeostasis, reactive oxygen species (ROS) production, calcium buffering, and intracellular signaling [41–44].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [42]
The review describes mitochondrial calcium buffering in neurons (Mitochondria in Ca²⁺ Homeostasis, p. 11), links mitochondrial calcium handling to ROS generation (p. 12), and describes a role in cellular calcium signaling (Introduction, p. 4). It does not establish the claim about neuronal redox homeostasis specifically; its redox discussion is not framed as a neuronal finding. (LLM, conf=0.84)
Experimental — accuracy not yet measuredExcessive Ca2+ levels in mitochondria activate pro-apoptotic pathways and affect mitochondrial metabolism, ATP production and neurotransmitters release at synaptic level, potentiating neurodegeneration.
“Excessive Ca2+ levels in mitochondria activate pro-apoptotic pathways [69] and affect mitochondrial metabolism, ATP production and neurotransmitters release at the synaptic level [70], potentiating neurodegeneration.”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [70]
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- Authors
- Giorgi, C., Marchi, S., & Pinton, P.
- Affiliations
- University of Ferrara (IT)
- Corresponding author
- Pinton, Paolo
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2018-08-24
- Volume
- 19
- Issue
- 11
- Pages
- 713-730
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2888403478
- Cited by
- 941
- References
- 11
- Citations by year
- 2026: 158 · 2025: 143 · 2024: 148 · 2023: 114 · 2022: 102 · 2021: 112 · 2020: 100 · 2019: 60 · 2018: 4
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-09-24)
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- mitochondrial calcium, mitochondrial calcium uptake, mitochondrial calcium efflux, calcium homeostasis, mitochondrial calcium uniporter, mitochondrial calcium signaling, mitochondrial metabolism, ATP production, cell death
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