The multifunctional nature of mitochondrial contact site proteins

Harper, Clare S.; White, Antoineen J.; Lackner, Laura L.

doi:10.1016/j.ceb.2020.02.010

Cited by 27 publications

(18 citation statements)

References 48 publications

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“…First, the mitochondrial network provides a large surface area for signal amplification. Second and possibly even more relevant, mitochondria are highly dynamic and mobile organelles that engage in physical and functional interactions with other organelles and the plasma membrane (Giacomello et al, 2020; Harper et al, 2020 ; Prinz et al, 2020; Scorrano et al, 2019). We therefore wondered whether mitochondria facilitate the transport of activated NF-κB components to the nucleus.…”

Section: Resultsmentioning

confidence: 99%

LUBAC assembles a signaling platform at mitochondria for signal amplification and shuttling of NF-ĸB to the nucleus

Berlemann

Bader

et al. 2022

Preprint

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Mitochondria are increasingly recognized as cellular hubs to orchestrate signaling pathways that regulate metabolism, redox homeostasis, and cell fate decisions. Recent research revealed a role of mitochondria also in innate immune signaling, however, the mechanisms of how mitochondria affect signal transduction are poorly understood. Here we show that the NF-ĸB pathway activated by TNF employs mitochondria as a platform for signal amplification and shuttling of activated NF-ĸB to the nucleus. TNF induces the recruitment of HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), and its substrate NEMO to the outer mitochondrial membrane, where M1- and K63-linked ubiquitin chains are generated. NF-ĸB is locally activated and transported to the nucleus by mitochondria, resulting in an increase in mitochondria-nucleus contact sites in a HOIP-dependent manner. Notably, TNF-induced stabilization of the mitochondrial kinase PINK1 contributes to signal amplification by antagonizing the M1-ubiquitin-specific deubiquitinase OTULIN.

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Section: Resultsmentioning

confidence: 99%

LUBAC assembles a signaling platform at mitochondria for signal amplification and shuttling of NF-ĸB to the nucleus

Berlemann

Bader

et al. 2022

Preprint

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“…In conclusion, [Ca 2+ ] i modulated by SOCE is a master physiological regulator that contributes to uncontrolled proliferation and malignant tumor progression ( Sharma and Elble, 2020 ). We must recall that mitochondrial Ca 2+ activates the Krebs cycle, apoptosis, and mitochondrial fission ( Harper et al, 2020 ). In particular, the activity of α-ketoglutarate, isocitrate, and pyruvate dehydrogenases is controlled by the cation, increasing the ATP synthesis.…”

Section: Regulated Cellular Processes At Contact Sites and Their Relamentioning

confidence: 99%

Relevance of Membrane Contact Sites in Cancer Progression

Gil-Hernández

Arroyo-Campuzano

Simoni‐Nieves

et al. 2021

Front. Cell Dev. Biol.

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Membrane contact sites (MCS) are typically defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins. The study of MCS is considered as an emergent field that shows how crucial organelle interactions are in cell physiology. MCS regulate a myriad of physiological processes such as apoptosis, calcium, and lipid signaling, just to name a few. The membranal interactions between the endoplasmic reticulum (ER)–mitochondria, the ER–plasma membrane, and the vesicular traffic have received special attention in recent years, particularly in cancer research, in which it has been proposed that MCS regulate tumor metabolism and fate, contributing to their progression. However, as the therapeutic or diagnostic potential of MCS has not been fully revisited, in this review, we provide recent information on MCS relevance on calcium and lipid signaling in cancer cells and on its role in tumor progression. We also describe some proteins associated with MCS, like CERT, STIM1, VDAC, and Orai, that impact on cancer progression and that could be a possible diagnostic marker. Overall, these information might contribute to the understanding of the complex biology of cancer cells.

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“…Thus, mitochondrial reorganization is an integral part of the control of cell cycle progression. Interestingly, mitochondrial architecture, or more specifically, tethering of mitochondria to the plasma membrane, is important for spindle organization in budding yeast [ 121 , 122 ], where distribution of mitochondria between mother and bud is a highly regulated process. In higher eukaryotes, where mitochondria are randomly distributed among daughter cells, fragmented mitochondria migrate to the division furrow immediately before cytokinesis in a process dominated by plasma membrane-mitochondrial contacts [ 123 ].…”

Section: Mitochondrial Architecture Dynamics and Morphology In Normal Cellsmentioning

confidence: 99%

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

Pedersen

Flinck

Pardo

2021

IJMS

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Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and mitochondrial phenotype undergo pervasive changes during cancer development, and both play key roles in driving the malignancy. However, the link between these events has been largely ignored. This review comprehensively summarizes and critically discusses the role of the reciprocal relationship between ion transport and mitochondria in crucial cellular functions, including metabolism, signaling, and cell fate decisions. We focus on Ca2+, H+, and K+, which play essential and highly interconnected roles in mitochondrial function and are profoundly dysregulated in cancer. We describe the transport and roles of these ions in normal mitochondria, summarize the changes occurring during cancer development, and discuss how they might impact tumorigenesis.

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The multifunctional nature of mitochondrial contact site proteins

Cited by 27 publications

References 48 publications

LUBAC assembles a signaling platform at mitochondria for signal amplification and shuttling of NF-ĸB to the nucleus

LUBAC assembles a signaling platform at mitochondria for signal amplification and shuttling of NF-ĸB to the nucleus

Relevance of Membrane Contact Sites in Cancer Progression

The Interplay between Dysregulated Ion Transport and Mitochondrial Architecture as a Dangerous Liaison in Cancer

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