Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar 11;21(6):1905.
doi: 10.3390/ijms21061905.

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Stefania Martucciello  1 , Milena Masullo  2 , Antonietta Cerulli  2 , Sonia Piacente  2
Affiliations
Review

Natural Products Targeting ER Stress, and the Functional Link to Mitochondria

Stefania Martucciello et al. Int J Mol Sci. .

Abstract

The endoplasmic reticulum (ER) is a dynamic organelle essential for intracellular homeostasis maintenance, controlling synthesis, the folding of secreted and membrane-bound proteins, and transport of Ca2+. During cellular stress, ER dysfunction leads to the activation of unfolded protein response (UPR) due to accumulated misfolded proteins in the ER. This condition is referred as ER stress. Mitochondria and ER form a site of close contact (the mitochondria-associated membrane, MAM) which is a major platform exerting important physiological roles in the regulation of intracellular Ca2+ homeostasis, lipid metabolism, mitochondrial fission, autophagosome formation, and apoptosis progression. Natural products have been receiving increasing attention for their ability to interfere with ER stress. Research works have focused on the capacity of these bioactive compounds to induce apoptosis by activating ER stress through the ER stress-mediated mitochondrial apoptotic pathway. In this review we discuss the role of natural products in the signaling communication between ER and mitochondria, focusing on the effects induced by ER stress including Ca2+ permeability transition and UPR signaling (protein kinase R-like ER kinase/mitofusin 2).

Keywords: Ca2+ permeability transition; ER stress; apoptosis; mitochondria; natural products; unfolded protein response.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The endoplasmic reticulum (ER) signaling pathway and the ER–mitochondria pathway triggered by natural compounds.
Figure 2
Figure 2
Natural compounds acting on the signaling communication between the ER and mitochondria.
Figure 3
Figure 3
Natural products targeting mitochondria-associated membranes.
See this image and copyright information in PMC

References

    1. Lin J.H., Walter P., Yen T.S. Endoplasmic reticulum stress in disease pathogenesis. Annu. Rev. Pathol. 2008;3:399–425. doi: 10.1146/annurev.pathmechdis.3.121806.151434. - DOI - PMC - PubMed
    1. Ma Y., Hendershot L.M. The role of the unfolded protein response in tumour development: Friend or foe? Nat. Rev. Cancer. 2004;4:966–977. doi: 10.1038/nrc1505. - DOI - PubMed
    1. Kincaid M.M., Cooper A.A. Misfolded proteins traffic from the endoplasmic reticulum (ER) due to ER export signals. Mol. Biol. Cell. 2007;18:455–463. doi: 10.1091/mbc.e06-08-0696. - DOI - PMC - PubMed
    1. Kim I., Xu W.J., Reed J.C. Cell death and endoplasmic reticulum stress: Disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 2008;7:1013–1030. doi: 10.1038/nrd2755. - DOI - PubMed
    1. Amodio G., Moltedo O., Fasano D., Zerillo L., Oliveti M., Di Pietro P., Faraonio R., Barone P., Pellecchia M.T., De Rose A., et al. PERK-Mediated Unfolded Protein Response Activation and Oxidative Stress in PARK20 Fibroblasts. Front. Neurosci-Switz. 2019;13 doi: 10.3389/fnins.2019.00673. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources