Control of Mitochondrial Activity by the Ubiquitin Code in Health and Cancer

Abstract

Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, undergoing programmed death when a serious, irreversible damage occurs. The key element of a functional integration of all these processes is the correct crosstalk between cell signaling and mitochondrial activities. Once this crosstalk is interrupted, the cell is not able to communicate its needs to mitochondria, resulting in oxidative stress and development of pathological conditions. Conversely, dysfunctional mitochondria may affect cell viability, even in the presence of nutrients supply and energy production, indicating the existence of feed-back control mechanisms between mitochondria and other cellular compartments. The ubiquitin proteasome system (UPS) is a multi-step biochemical pathway that, through the conjugation of ubiquitin moieties to specific protein substrates, controls cellular proteostasis and signaling, removing damaged or aged proteins that might otherwise accumulate and affect cell viability. In response to specific needs or changed extracellular microenvironment, the UPS modulates the turnover of mitochondrial proteins, thus influencing the organelle shape, dynamics and function. Alterations of the dynamic and reciprocal regulation between mitochondria and UPS underpin genetic and proliferative disorders. This review focuses on the mitochondrial metabolism and activities supervised by UPS and examines how deregulation of this control mechanism results in proliferative disorders and cancer.

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

“…Cell viability is a critical parameter for assessing the health and functionality of cells when exposed to various assaults determined through the utilization of the MTT assay, which evaluates mitochondrial activity 51 . In the current investigation, the cell viability of the optimized TPs, particularly M1, M3, and M6, was evaluated at 24-, 48-, and 72 h intervals and compared to a control group displaying acceptable (~ 80%) cell viability (Fig.…”

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

“…Mitochondrial dysfunction is key for neurodegenerative diseases [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ]. Mitochondria are at the core of cellular energy production and interruption of the crosstalk between cell signaling and mitochondrial functions and biogenesis, and result in mitochondrial dysfunction, proteotoxic stress, accumulation of defective mitochondria, and the production of reactive oxygen species due to defective mitophagy and major alterations in the ubiquitin–proteasome system [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ,…”

“…Failure to accomplish perfect mitochondrial quality control mechanisms has fatal brain consequences [ 104 , 105 ]. Abnormalities in the ubiquitin–proteasome system and mitophagy result in defects of brain energy translocation and accumulation of the byproducts of oxidative stress [ 104 , 105 , 106 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ].…”

Orchestration of Mitochondrial Function and Remodeling by Post-Translational Modifications Provide Insight into Mechanisms of Viral Infection

“…Post-translational regulation of protein function is often dictated by the competition of PTM "writers" and "erasers" over the protein substrate: phosphorylation through kinases and phosphatases, acetylation through acetyltransferases and deacetylases, and ubiquitination through ubiquitin ligases and deubiquitinases [216]. This paradigm extends to the mitochondrial proteome for many PTMs, such as the pyruvate dehydrogenase kinases and phosphatases regulating PDH activity [77,[217][218][219].…”