Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics
Open accessAbstract
Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER-mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders.
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Thapsigargin-induced Ca2+ transfer from the ER to mitochondria depends on IP3R in the ER and VDACs on the outer mitochondrial membrane.
“Furthermore, thapsigargin-induced Ca2+ transfer from the ER to mitochondria depends on IP3R in the ER and VDACs on the outer mitochondrial membrane [93, 94].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [94]
Section 2.2 identifies IP3R and VDAC as the main ER–mitochondria Ca2+ transfer channels on the ER and mitochondrial sides, respectively. Section 3 describes mitochondrial uptake of Ca2+ released through ER-localized IP3R. The copy does not establish that thapsigargin-induced transfer specifically depends on both channels. (LLM, conf=0.86)
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Cites
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- Authors
- Bravo, R., Gutierrez, T., Paredes, F., Gatica, D., Rodriguez, A. E., Pedrozo, Z., Chiong, M., Parra, V., Quest, A. F. G., Rothermel, B. A., & Lavandero, S.
- Affiliations
- University of Chile (CL)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Rothermel, Beverly A.
- Lavandero, Sergio
- ORCID
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 44
- Issue
- 1
- Pages
- 16-20
- ISSN
- 1357-2725 (ISSN-L)
- PMC
- PMC4118286
- OpenAlex
- W2037525354
- Cited by
- 191
- References
- 1
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 10 · 2023: 10 · 2022: 15 · 2021: 26 · 2020: 13 · 2019: 13 · 2018: 9 · 2017: 15 · 2016: 14 · 2015: 12 · 2014: 12 · 2013: 15 · 2012: 10
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Universidad de Chile (submittedVersion)
- Funders
- Comision Nacional de Ciencia y Tecnologia (CONICYT), Chile (FONDECYT 1080436, FONDECYT 1110180, FONDECYT 3110039, FONDAP 15010006)
- National Institutes of Health (HL072016, HL097768)
- American Heart Association (0655202Y)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- endoplasmic reticulum stress, unfolded protein response, mitochondrial bioenergetics, ER-mitochondria communication, calcium transfer, mitochondrial calcium homeostasis, apoptosis, metabolic disorders
- MeSH terms
- Endoplasmic Reticulum, Energy Metabolism, Humans, Mitochondria, Endoplasmic Reticulum Stress
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