scholarly journals Cross Talk of Proteostasis and Mitostasis in Cellular Homeodynamics, Ageing, and Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-24 ◽  
Author(s):  
Sentiljana Gumeni ◽  
Ioannis P. Trougakos
Keyword(s):  
Quality Control ◽  
Cross Talk ◽  
Ubiquitin Proteasome System ◽  
Eukaryotic Cell ◽  
Integrated System ◽  
Mitochondrial Quality Control ◽  
Metabolic Functions ◽  
Age Related ◽  
Ubiquitin Proteasome ◽  
Different Levels

Mitochondria are highly dynamic organelles that provide essential metabolic functions and represent the major bioenergetic hub of eukaryotic cell. Therefore, maintenance of mitochondria activity is necessary for the proper cellular function and survival. To this end, several mechanisms that act at different levels and time points have been developed to ensure mitochondria quality control. An interconnected highly integrated system of mitochondrial and cytosolic chaperones and proteases along with the fission/fusion machinery represents the surveillance scaffold of mitostasis. Moreover, nonreversible mitochondrial damage targets the organelle to a specific autophagic removal, namely, mitophagy. Beyond the organelle dynamics, the constant interaction with the ubiquitin-proteasome-system (UPS) has become an emerging aspect of healthy mitochondria. Dysfunction of mitochondria and UPS increases with age and correlates with many age-related diseases including cancer and neurodegeneration. In this review, we discuss the functional cross talk of proteostasis and mitostasis in cellular homeodynamics and the impairment of mitochondrial quality control during ageing, cancer, and neurodegeneration.

Mitochondrial quality control by the ubiquitin–proteasome system

2011 ◽  
Vol 39 (5) ◽  
pp. 1509-1513 ◽  
Author(s):  
Eric B. Taylor ◽  
Jared Rutter
Keyword(s):  
Quality Control ◽  
Ubiquitin Ligase ◽  
Protein Quality ◽  
Mitochondrial Protein ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Quality Control ◽  
Ubiquitinated Proteins ◽  
Ubiquitin Proteasome

Mitochondria perform multiple functions critical to the maintenance of cellular homoeostasis and their dysfunction leads to disease. Several lines of evidence suggest the presence of a MAD (mitochondria-associated degradation) pathway that regulates mitochondrial protein quality control. Internal mitochondrial proteins may be retrotranslocated to the OMM (outer mitochondrial membrane), multiple E3 ubiquitin ligases reside at the OMM and inhibition of the proteasome causes accumulation of ubiquitinated proteins at the OMM. Reminiscent of ERAD [ER (endoplasmic reticulum)-associated degradation], Cdc48 (cell division cycle 42)/p97 is recruited to stressed mitochondria, extracts ubiquitinated proteins from the OMM and presents ubiquitinated proteins to the proteasome for degradation. Recent research has provided mechanistic insights into the interaction of the UPS (ubiquitin–proteasome system) with the OMM. In yeast, Vms1 [VCP (valosin-containing protein) (p97)/Cdc48-associated mitochondrial-stress-responsive 1] protein recruits Cdc48/p97 to the OMM. In mammalian systems, the E3 ubiquitin ligase parkin regulates the recruitment of Cdc48/p97 to mitochondria, subsequent mitochondrial protein degradation and mitochondrial autophagy. Disruption of the Vms1 or parkin systems results in the hyper-accumulation of ubiquitinated proteins at mitochondria and subsequent mitochondrial dysfunction. The emerging MAD pathway is important for the maintenance of cellular and therefore organismal viability.

scholarly journals Mitochondrial Quality Control in the Maintenance of Cardiovascular Homeostasis: The Roles and Interregulation of UPS, Mitochondrial Dynamics and Mitophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yujie Song ◽  
Yuerong Xu ◽  
Yingying Liu ◽  
Jie Gao ◽  
Lele Feng ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dynamics ◽  
Ubiquitin Proteasome System ◽  
Normal Function ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Dynamic ◽  
Profound Influence ◽  
Ubiquitin Proteasome ◽  
And Function ◽  
The Relationship

Maintenance of normal function of mitochondria is vital to the fate and health of cardiomyocytes. Mitochondrial quality control (MQC) mechanisms are essential in governing mitochondrial integrity and function. The ubiquitin-proteasome system (UPS), mitochondrial dynamics, and mitophagy are three major components of MQC. With the progress of research, our understanding of MQC mechanisms continues to deepen. Gradually, we realize that the three MQC mechanisms are not independent of each other. To the contrary, there are crosstalk among the mechanisms, which can make them interact with each other and cooperate well, forming a triangle interplay. Briefly, the UPS system can regulate the level of mitochondrial dynamic proteins and mitophagy receptors. In the process of Parkin-dependent mitophagy, the UPS is also widely activated, performing critical roles. Mitochondrial dynamics have a profound influence on mitophagy. In this review, we provide new processes of the three major MQC mechanisms in the background of cardiomyocytes and delve into the relationship between them.

scholarly journals TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment

2021 ◽  
Author(s):  
Xu Zhou ◽  
Xiongjin Chen ◽  
Tingting Hong ◽  
Miaoping Zhang ◽  
Yujie Cai ◽  
...  
Keyword(s):  
Quality Control ◽  
Cognitive Impairment ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Research Progress ◽  
Repeat Domain ◽  
Ubiquitin Proteasome ◽  
Domain 3

AbstractThe tetrapeptide repeat domain 3 (TTC3) gene falls within Down's syndrome (DS) critical region. Cognitive impairment is a common phenotype of DS and Alzheimer’s disease (AD), and overexpression of TTC3 can accelerate cognitive decline, but the specific mechanism is unknown. The TTC3-mediated protein quality control (PQC) mechanism, similar to the PQC system, is divided into three parts: it acts as a cochaperone to assist proteins in folding correctly; it acts as an E3 ubiquitin ligase (E3s) involved in protein degradation processes through the ubiquitin–proteasome system (UPS); and it may also eventually cause autophagy by affecting mitochondrial function. Thus, this article reviews the research progress on the structure, function, and metabolism of TTC3, including the recent research progress on TTC3 in DS and AD; the role of TTC3 in cognitive impairment through PQC in combination with the abovementioned attributes of TTC3; and the potential targets of TTC3 in the treatment of such diseases.

scholarly journals Role of the ISR-ATF4 pathway and its cross talk with Nrf2 in mitochondrial quality control

2019 ◽  
Vol 64 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Shuya Kasai ◽  
Hiromi Yamazaki ◽  
Kunikazu Tanji ◽  
Máté János Engler ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Quality Control ◽  
Cross Talk ◽  
Mitochondrial Quality Control

Protein Quality Control in Neurodegeneration and Neuroprotection

2020 ◽  
pp. 1-24
Author(s):  
Yasmeena Akhter ◽  
Jahangir Nabi ◽  
Hinna Hamid ◽  
Nahida Tabassum ◽  
Faheem Hyder Pottoo ◽  
...  
Keyword(s):  
Quality Control ◽  
Neurodegenerative Disorders ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Security System ◽  
Conformational Disorders ◽  
Ubiquitin Proteasome ◽  
Multi Level

Proteostasis is essential for regulating the integrity of the proteome. Disruption of proteostasis under some rigorous conditions leads to the aggregation and accumulation of misfolded toxic proteins, which plays a central role in the pathogenesis of protein conformational disorders. The protein quality control (PQC) system serves as a multi-level security system to shield cells from abnormal proteins. The intrinsic PQC systems maintaining proteostasis include the ubiquitin-proteasome system (UPS), chaperon-mediated autophagy (CMA), and autophagy-lysosome pathway (ALP) that serve to target misfolded proteins for unfolding, refolding, or degradation. Alterations of PQC systems in neurons have been implicated in the pathogenesis of various neurodegenerative disorders. This chapter provides an overview of PQC pathways to set a framework for discussion of the role of PQC in neurodegenerative disorders. Additionally, various pharmacological approaches targeting PQC are summarized.

scholarly journals Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

2015 ◽  
Vol 35 (13) ◽  
pp. 2254-2264 ◽  
Author(s):  
Khalid Amine Timani ◽  
Ying Liu ◽  
Yan Fan ◽  
Khalid S. Mohammad ◽  
Johnny J. He
Keyword(s):  
Cross Talk ◽  
Hypoxia Inducible Factor ◽  
Ubiquitin Proteasome System ◽  
Metastatic Progression ◽  
Hypoxia Inducible Factor 1Α ◽  
Important Mediator ◽  
P300 Binding ◽  
Ubiquitin Proteasome ◽  
The Cross ◽  
Hypoxic Region

Hypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1α (HIF-1α), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1α. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1α was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1α in response to hypoxic stress.

Quality Control of Gastric Proton Pump in the Endoplasmic Reticulum by Ubiquitin/Proteasome System

2003 ◽  
Vol 986 (1) ◽  
pp. 655-657
Author(s):  
SHINJI ASANO ◽  
TOHRU KIMURA ◽  
HOKARA ISHIZUKA ◽  
MAGOTOSHI MORII ◽  
NORIAKI TAKEGUCHI
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Proton Pump ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome ◽  
Gastric Proton Pump
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