scholarly journals Inter-Organelle Membrane Contact Sites and Mitochondrial Quality Control during Aging: A Geroscience View

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 598 ◽  
Author(s):  
Anna Picca ◽  
Riccardo Calvani ◽  
Hélio José Coelho-Junior ◽  
Francesco Landi ◽  
Roberto Bernabei ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Age Related ◽  
Bidirectional Communication ◽  
Membrane Contact ◽  
Organelle Membrane

Mitochondrial dysfunction and failing mitochondrial quality control (MQC) are major determinants of aging. Far from being standalone organelles, mitochondria are intricately related with cellular other compartments, including lysosomes. The intimate relationship between mitochondria and lysosomes is reflected by the fact that lysosomal degradation of dysfunctional mitochondria is the final step of mitophagy. Inter-organelle membrane contact sites also allow bidirectional communication between mitochondria and lysosomes as part of nondegradative pathways. This interaction establishes a functional unit that regulates metabolic signaling, mitochondrial dynamics, and, hence, MQC. Contacts of mitochondria with the endoplasmic reticulum (ER) have also been described. ER-mitochondrial interactions are relevant to Ca2+ homeostasis, transfer of phospholipid precursors to mitochondria, and integration of apoptotic signaling. Many proteins involved in mitochondrial contact sites with other organelles also participate to degradative MQC pathways. Hence, a comprehensive assessment of mitochondrial dysfunction during aging requires a thorough evaluation of degradative and nondegradative inter-organelle pathways. Here, we present a geroscience overview on (1) degradative MQC pathways, (2) nondegradative processes involving inter-organelle tethering, (3) age-related changes in inter-organelle degradative and nondegradative pathways, and (4) relevance of MQC failure to inflammaging and age-related conditions, with a focus on Parkinson’s disease as a prototypical geroscience condition.

scholarly journals Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue

2021 ◽  
Vol 22 (6) ◽  
pp. 2881
Author(s):  
Clara Lefranc ◽  
Malou Friederich-Persson ◽  
Fabienne Foufelle ◽  
Aurélie Nguyen Dinh Cat ◽  
Frédéric Jaisser
Keyword(s):  
Quality Control ◽  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Cellular Senescence ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Oxidative Stress ◽  
Specific Effects

Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity.

scholarly journals Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites

2016 ◽  
Vol 27 (15) ◽  
pp. 2435-2449 ◽  
Author(s):  
Jae-Sook Park ◽  
Mary K. Thorsness ◽  
Robert Policastro ◽  
Luke L. McGoldrick ◽  
Nancy M. Hollingsworth ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Protein Sorting ◽  
Growth Conditions ◽  
Eukaryotic Cells ◽  
Cellular Functions ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

The Vps13 protein family is highly conserved in eukaryotic cells. Mutations in human VPS13 genes result in a variety of diseases, such as chorea acanthocytosis (ChAc), but the cellular functions of Vps13 proteins are not well defined. In yeast, there is a single VPS13 orthologue, which is required for at least two different processes: protein sorting to the vacuole and sporulation. This study demonstrates that VPS13 is also important for mitochondrial integrity. In addition to preventing transfer of DNA from the mitochondrion to the nucleus, VPS13 suppresses mitophagy and functions in parallel with the endoplasmic reticulum–mitochondrion encounter structure (ERMES). In different growth conditions, Vps13 localizes to endosome–mitochondrion contacts and to the nuclear–vacuole junctions, indicating that Vps13 may function at membrane contact sites. The ability of VPS13 to compensate for the absence of ERMES correlates with its intracellular distribution. We propose that Vps13 is present at multiple membrane contact sites and that separation-of-function mutants are due to loss of Vps13 at specific junctions. Introduction of VPS13A mutations identified in ChAc patients at cognate sites in yeast VPS13 are specifically defective in compensating for the lack of ERMES, suggesting that mitochondrial dysfunction might be the basis for ChAc.

Disturbed mitochondrial quality control involved in hepatocytotoxicity induced by silica nanoparticles

Nanoscale ◽  
2020 ◽  
Vol 12 (24) ◽  
pp. 13034-13045 ◽  
Author(s):  
Yi Qi ◽  
Ru Ma ◽  
Xueyan Li ◽  
Songqing Lv ◽  
Xiaoying Liu ◽  
...  
Keyword(s):  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Silica Nanoparticles ◽  
Cell Damage ◽  
Mitochondrial Dynamics ◽  
Control Process ◽  
Mitochondrial Quality Control ◽  
Quality Control Process

SiNPs triggered hepatocytotoxicity through interfering mitochondrial quality control process, including imbalanced mitochondrial dynamics, disturbed mitophagy and suppressed biogenesis, leading to mitochondrial dysfunction and ensuing cell damage.

scholarly journals Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xue Jiang ◽  
Tao Jin ◽  
Haining Zhang ◽  
Jing Miao ◽  
Xiuzhen Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Dynamics ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Toxic Metabolite ◽  
Mitochondrial Quality Control

Parkinson’s disease (PD), clinically characterized by motor and nonmotor symptoms, is a common progressive and multisystem neurodegenerative disorder, which is caused by both genetic and environmental risk factors. The main pathological features of PD are the loss of dopaminergic (DA) neurons and the accumulation of alpha-synuclein (α-syn) in the residual DA neurons in the substantia nigra pars compacta (SNpc). In recent years, substantial progress has been made in discovering the genetic factors of PD. In particular, a total of 19 PD-causing genes have been unraveled, among which some members have been regarded to be related to mitochondrial dysfunction. Mitochondria are key regulators of cellular metabolic activity and are critical for many important cellular processes including energy metabolism and even cell death. Their normal function is basically maintained by the mitochondrial quality control (MQC) mechanism. Accordingly, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a kind of neurotoxin, exerts its neurotoxic effects at least partially by producing its toxic metabolite, namely, 1-methyl-4-phenylpyridine (MPP+), which in turn causes mitochondrial dysfunction by inhibiting complex I and mimicking the key features of PD pathogenesis. This review focused on three main aspects of the MQC signaling pathways, that is, mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy; hence, it demonstrates in detail how genetic and environmental factors result in PD pathogenesis by interfering with MQC pathways, thereby hopefully contributing to the discovery of novel potential therapeutic targets for PD.

scholarly journals Inter-organelle membrane contact sites: implications for lipid metabolism

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jean E. Vance
Keyword(s):  
Endoplasmic Reticulum Membrane ◽  
Biological Functions ◽  
Advantages And Disadvantages ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Experimental Approaches ◽  
Initial Discovery ◽  
Membrane Contact ◽  
Definition Of ◽  
Organelle Membrane

Abstract This article supplements a recent Perspective by Scorrano et al. in Nature Communications [10 [ (1)]:1287] in which the properties and functions of inter-organelle membrane contact sites were summarized. It is now clear that inter-organelle membrane contact sites are widespread in eukaryotic cells and that diverse pairs of organelles can be linked via unique protein tethers. An appropriate definition of what constitutes an inter-organelle membrane contact site was proposed in the Perspective. In addition, the various experimental approaches that are frequently used to study these organelle associations, as well as the advantages and disadvantages of each of these methods, were considered. The nature of the tethers that link the pairs of organelles at the contact sites was discussed in detail and some biological functions that have been ascribed to specific membrane contact sites were highlighted. Nevertheless, the functions of most types of organelle contact sites remain unclear. In the current article I have considered some of the points raised in the Perspective but have omitted detailed information on the roles of membrane contact sites in biological functions such as apoptosis, autophagy, calcium homeostasis and mitochondrial fusion. Instead, I have provided some background on the initial discovery of mitochondria-endoplasmic reticulum membrane contact sites, and have focussed on the known roles of membrane contact sites in inter-organelle lipid transport. In addition, potential roles for membrane contact sites in human diseases are briefly discussed.

scholarly journals Peroxisome biogenesis, membrane contact sites, and quality control

EMBO Reports ◽  
2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Jean‐Claude Farré ◽  
Shanmuga S Mahalingam ◽  
Marco Proietto ◽  
Suresh Subramani
Keyword(s):  
Quality Control ◽  
Peroxisome Biogenesis ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact
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