Interplay between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis

Escobar-Henriques, Mafalda; Altin, Selver; Brave, Fabian den

doi:10.21775/cimb.035.035

Cited by 17 publications

(19 citation statements)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported studies support the idea that ubiquitin-dependent mitochondrial quality control pathways efficiently adapt in response to environmental and metabolic changes. However, in case of acute stress conditions, specialized response programs are induced to adjust the UPS capacity and thereby restore organellar proteostasis (Pakos-Zebrucka et al, 2016;Braun and Westermann, 2017;D'Amico et al, 2017;Pickles et al, 2018;Andréasson et al, 2019;Zheng et al, 2019;Escobar-Henriques et al, 2020). Besides understanding the mechanistic details of individual pathways, the regulation of cell-type specific and organismal composition of mitochondrial quality control need to be further addressed.…”

Section: Resultsmentioning

confidence: 99%

“…Mitochondria are equipped with an elaborate set of proteases acting on the different sub-compartments, to maintain the mitochondrial proteome from the inside (Koppen and Langer, 2007;Quirós et al, 2015;Glynn, 2017). Otherwise, the integrity of the mitochondrial proteome is largely supported by the UPS localized in the cytosol (Franz et al, 2015;Bragoszewski et al, 2017;Braun and Westermann, 2017;D'Amico et al, 2017;Escobar-Henriques et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mitochondria are essential organelles important for energy production, proliferation, and cell death. Biogenesis, homeostasis, and degradation of this organelle are tightly controlled to match cellular needs and counteract chronic stress conditions. Despite providing their own DNA, the vast majority of mitochondrial proteins are encoded in the nucleus, synthesized by cytosolic ribosomes, and subsequently imported into different mitochondrial compartments. The integrity of the mitochondrial proteome is permanently challenged by defects in folding, transport, and turnover of mitochondrial proteins. Therefore, damaged proteins are constantly sequestered from the outer mitochondrial membrane and targeted for proteasomal degradation in the cytosol via mitochondrial-associated degradation (MAD). Recent studies identified specialized quality control mechanisms important to decrease mislocalized proteins, which affect the mitochondrial import machinery. Interestingly, central factors of these ubiquitindependent pathways are shared with the ER-associated degradation (ERAD) machinery, indicating close collaboration between both tubular organelles. Here, we summarize recently described cellular stress response mechanisms, which are triggered by defects in mitochondrial protein import and quality control. Moreover, we discuss how ubiquitindependent degradation is integrated with cytosolic stress responses, particularly focused on the crosstalk between MAD and ERAD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…An elaborate set of proteins localizing to both the mitochondrial inner and outer membrane regulates dynamics of the mitochondrial network and in turn bioenergetics [66,71]. As mentioned above, the turnover of many of these proteins is regulated by UPS [26,31,39]. Thus, it is apparent that UPS regulates mitochondrial bioenergetics indirectly through modulation of mitochondrial network dynamics.…”

Section: Implications Of Intramitochondrial Protein Ubiquitination: Mmentioning

confidence: 99%

“…The fusion machinery constitutes multiple GTPases: MFN1, MFN2 and OPA1; whereas the fission machinery relies on a cytosolic GTPase DRP1 which interacts with receptor proteins on the OMM such as MFF, FIS-1, MID49 and MID51 [36,37]. Levels of many individual components of this machinery are regulated by selective ubiquitin-proteasome turnover [31,33,34,38,39]. Mitochondrial dynamics serve as a mechanism to preserve healthy mitochondria via fusion and eliminate the damaged ones by fission, subsequently subjecting them to removal by mitochondria autophagy (mitophagy) [40].…”

Section: Introduction -Modes Of Mitochondrial Protein Quality Controlmentioning

confidence: 99%

Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

Sulkshane

Ram

Glickman

2020

Preprint

View full text Add to dashboard Cite

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The Ubiquitin-Proteasome System (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the ER and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination have remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for the basal function of mitochondria, metabolic implications, and possible therapeutic applications.

show abstract

“…By serving as a cell death gatekeeper, mitochondria play a central role in cellular quality control and survival decisions. Here, formation of the mitochondrial permeability transition pore and ERAD, Cdc48/p97 and the proteasome assist mitochondrial-associated degradation (MAD) [29,[64][65][66][67] ( Figure 1). Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

Escobar-Henriques

Anton

2020

IJMS

Self Cite

View full text Add to dashboard Cite

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. The role of Cdc48/p97 in endoplasmic reticulum-associated degradation (ERAD), where it extracts proteins targeted for degradation from the ER membrane, has been extensively described. Here, we present the roles of Cdc48/p97 in mitochondrial regulation. We discuss mitochondrial quality control surveillance by Cdc48/p97 in mitochondrial-associated degradation (MAD), highlighting the potential pathologic significance thereof. Furthermore, we present the current knowledge of how Cdc48/p97 regulates mitofusin activity in outer membrane fusion and how this may impact on neurodegeneration.

show abstract

Interplay between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis

Cited by 17 publications

References 175 publications

Mitochondrial Quality Control Governed by Ubiquitin

Mitochondrial Quality Control Governed by Ubiquitin

Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

Contact Info

Product

Resources

About