The mystery of mitochondria-ER contact sites in physiology and pathology: A cancer perspective

Simões, Inês C M; Morciano, Giampaolo; Lebiedzińska-Arciszewska, Magdalena; Aguiari, Gianluca; Pinton, Paolo; Potes, Yaiza; Wieckowski, Mariusz R.

doi:10.1016/j.bbadis.2020.165834

Cited by 58 publications

(62 citation statements)

References 249 publications

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“…Similar approaches suggest that a quick change of nuclear shape could induce breaks of the nuclear envelope after sudden change of the shape of the nuclear envelope, i.e., during movements of cells through narrow channels. Similarly, the fusion of mitochondria generates an excess of the surface area of the outer mitochondrial membrane, whereas their fission needs the delivery of new lipid molecules to the outer mitochondria membrane through ER-mitochondria contact sites [ 95 , 96 , 97 ].…”

Section: Discussionmentioning

confidence: 99%

Membrane Curvature, Trans-Membrane Area Asymmetry, Budding, Fission and Organelle Geometry

Mirоnоv

Mironov

Derganc

et al. 2020

IJMS

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In biology, the modern scientific fashion is to mostly study proteins. Much less attention is paid to lipids. However, lipids themselves are extremely important for the formation and functioning of cellular membrane organelles. Here, the role of the geometry of the lipid bilayer in regulation of organelle shape is analyzed. It is proposed that during rapid shape transition, the number of lipid heads and their size (i.e., due to the change in lipid head charge) inside lipid leaflets modulates the geometrical properties of organelles, in particular their membrane curvature. Insertion of proteins into a lipid bilayer and the shape of protein trans-membrane domains also affect the trans-membrane asymmetry between surface areas of luminal and cytosol leaflets of the membrane. In the cases where lipid molecules with a specific shape are not predominant, the shape of lipids (cylindrical, conical, or wedge-like) is less important for the regulation of membrane curvature, due to the flexibility of their acyl chains and their high ability to diffuse.

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Section: Discussionmentioning

confidence: 99%

Membrane Curvature, Trans-Membrane Area Asymmetry, Budding, Fission and Organelle Geometry

Mirоnоv

Mironov

Derganc

et al. 2020

IJMS

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“…Oncogenes and tumor suppressors can benefit from the MERCs functions, as this platform can promote metabolic reprograming, restriction or hyperactivation of Ca 2+ -dependent signaling, antioxidant response, and apoptosis (reviewed in [58,59]). This is supported by the findings that the products of oncogenes or tumor suppressors have been found at the mitochondria-ER interfaces [59,60].…”

Section: Mercs and Cancermentioning

confidence: 99%

“…The tumor suppressor p53 was also found at MERCs, where it regulates the activity of the sarco-endoplasmic reticulum Ca 2+ ATPase (SERCA), the pump responsible for Ca 2+ re-uptake into the ER upon its release into the cytosol [64]. Other examples of MERCs resident Ca 2+ modulators described with pro-and anti-oncogenic actions include phosphatase and tensin homolog (PTEN), breast cancer type 1 (BRCA1), and B-cell lymphoma 2 (BCL-2) (reviewed in [58]).…”

Section: Mercs and Cancermentioning

confidence: 99%

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Chemical Modulation of Mitochondria–Endoplasmic Reticulum Contact Sites

Rebelo

Bello

Knedlík

et al. 2020

Cells

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Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional complexity, their exploitation as pharmacological targets has never been considered so far. Notwithstanding, the number of compounds described to target proteins residing at these interfaces either directly or indirectly is rising. Here we provide original insight into mitochondria–ER contact sites (MERCs), with a comprehensive overview of the current MERCs pharmacology. Importantly, we discuss the considerable potential of MERCs to become a druggable target for the development of novel therapeutic strategies.

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“…Several oncoproteins can interact at the MAMs with the inositol 1,4,5-triphosphate receptor (IP3R) responsible for Ca 2+ release from the ER, and can thus modulate Ca 2+ fluxes to the mitochondria, with consequent regulation of the induction of the intrinsic apoptotic pathway. Recently, it has been demonstrated that all three IP3R isoforms are required for maintaining MERCs [ 47 ], and that IP3R can bind with proteins like the phosphatase and tensin homolog deleted on chromosome 10 (PTEN), breast cancer type 1 susceptibility protein (BRCA1) and Bcl-2 [ 48 ]. PTEN, often mutated or absent in several cancers, can physical interact with IP3R3, thus favoring Ca 2+ transfer by dephosphorylating both IP3R3 and AKT and leading to cell death [ 49 ].…”

Section: Mitochondria and Endoplasmic Reticulummentioning

confidence: 99%

Mitochondrial Metabolism, Contact Sites and Cellular Calcium Signaling: Implications for Tumorigenesis

Peruzzo

Costa

Bachmann

et al. 2020

Cancers

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Mitochondria are organelles that are mainly involved in the generation of ATP by cellular respiration. In addition, they modulate several intracellular functions, ranging from cell proliferation and differentiation to cell death. Importantly, mitochondria are social and can interact with other organelles, such as the Endoplasmic Reticulum, lysosomes and peroxisomes. This symbiotic relationship gives advantages to both partners in regulating some of their functions related to several aspects of cell survival, metabolism, sensitivity to cell death and metastasis, which can all finally contribute to tumorigenesis. Moreover, growing evidence indicates that modulation of the length and/or numbers of these contacts, as well as of the distance between the two engaged organelles, impacts both on their function as well as on cellular signaling. In this review, we discuss recent advances in the field of contacts and communication between mitochondria and other intracellular organelles, focusing on how the tuning of mitochondrial function might impact on both the interaction with other organelles as well as on intracellular signaling in cancer development and progression, with a special focus on calcium signaling.

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The mystery of mitochondria-ER contact sites in physiology and pathology: A cancer perspective

Cited by 58 publications

References 249 publications

Membrane Curvature, Trans-Membrane Area Asymmetry, Budding, Fission and Organelle Geometry

Membrane Curvature, Trans-Membrane Area Asymmetry, Budding, Fission and Organelle Geometry

Chemical Modulation of Mitochondria–Endoplasmic Reticulum Contact Sites

Mitochondrial Metabolism, Contact Sites and Cellular Calcium Signaling: Implications for Tumorigenesis

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