Emerging roles of mitochondrial membrane dynamics in health and disease

2009 ◽  
Vol 390 (8) ◽  
Author(s):  
Anja Schäfer ◽  
Andreas S. Reichert
Keyword(s):  
Quality Control ◽  
Molecular Basis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Dynamics ◽  
Physiological Role ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Mitochondrial Quality Control ◽  
Health And Disease

Abstract Mitochondria are highly dynamic organelles forming a tubular network that is sustained by fusion and fission events. Impairment thereof leads to various neuropathies in humans, such as optic atrophy and Parkinson's disease. We have only begun to understand the molecular machineries facilitating fusion and fission of mitochondria and how these processes are regulated. The physiological role of mitochondrial dynamics and how it may be involved in maintaining mitochondrial functionality is still unclear. Here, we discuss current views in this emerging field focusing on the molecular basis of how mitochondrial morphology is regulated and how this may contribute to mitochondrial quality control.

scholarly journals Mitochondrial Membrane Dynamics—Functional Positioning of OPA1

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 186 ◽  
Author(s):  
Hakjoo Lee ◽  
Yisang Yoon
Keyword(s):  
Mitochondrial Membrane ◽  
Proteolytic Cleavage ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Functional Differences ◽  
New Information ◽  
New Development

The maintenance of mitochondrial energetics requires the proper regulation of mitochondrial morphology, and vice versa. Mitochondrial dynamins control mitochondrial morphology by mediating fission and fusion. One of them, optic atrophy 1 (OPA1), is the mitochondrial inner membrane remodeling protein. OPA1 has a dual role in maintaining mitochondrial morphology and energetics through mediating inner membrane fusion and maintaining the cristae structure. OPA1 is expressed in multiple variant forms through alternative splicing and post-translational proteolytic cleavage, but the functional differences between these variants have not been completely understood. Recent studies generated new information regarding the role of OPA1 cleavage. In this review, we will first provide a brief overview of mitochondrial membrane dynamics by describing fission and fusion that are mediated by mitochondrial dynamins. The second part describes OPA1-mediated fusion and energetic maintenance, the role of OPA1 cleavage, and a new development in OPA1 function, in which we will provide new insight for what OPA1 does and what proteolytic cleavage of OPA1 is for.

Role of autophagy in cancer prevention, development and therapy

2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Anticancer Therapy ◽  
Substantial Progress ◽  
Health And Disease ◽  
Made In

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.

scholarly journals The Physiological Role of Mitophagy: New Insights into Phosphorylation Events

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yuko Hirota ◽  
Dongchon Kang ◽  
Tomotake Kanki
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Mitochondrial Dna ◽  
Control Systems ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Acid Oxidation ◽  
Molecular Processes ◽  
Mitochondrial Quality Control

Mitochondria play an essential role in oxidative phosphorylation, fatty acid oxidation, and the regulation of apoptosis. However, this organelle also produces reactive oxygen species (ROS) that continually inflict oxidative damage on mitochondrial DNA, proteins, and lipids, which causes further production of ROS. To oppose this oxidative stress, mitochondria possess quality control systems that include antioxidant enzymes and the repair or degradation of damaged mitochondrial DNA and proteins. If the oxidative stress exceeds the capacity of the mitochondrial quality control system, it seems that autophagy degrades the damaged mitochondria to maintain cellular homeostasis. Indeed, recent evidence from yeast to mammals indicates that the autophagy-dependent degradation of mitochondria (mitophagy) contributes to eliminate dysfunctional, aged, or excess mitochondria. In this paper, we describe the molecular processes and regulatory mechanisms of mitophagy in yeast and mammalian cells.

scholarly journals Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Dajun Zhao ◽  
Yang Sun ◽  
Yanzhen Tan ◽  
Zhengbin Zhang ◽  
Zuoxu Hou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Quality Control ◽  
Short Duration ◽  
Cardiac Dysfunction ◽  
Mitochondrial Dynamics ◽  
Left Ventricular ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Mitochondrial Quality Control ◽  
Aged Mice

Background. Exercise benefits to cardiac rehabilitation (CR) following stable myocardial infarction (MI). The suitable exercise duration for aged patients with coronary heart disease (CHD) remains controversial, and the underlying molecular mechanism is still unclear. Methods and Results. 18-Month-old mice after stable MI were randomly submitted to different durations of exercise, including 15 and 60 min swimming training (ST) once per day, five times a week for 8 weeks. Compared to sedentary mice, 15 min ST, rather than 60 min ST, significantly augmented left ventricular function, increased survival rate, and suppressed myocardial fibrosis and apoptosis. 15 min ST improved mitochondrial morphology via regulating mitochondrial fission-fusion signaling. 15 min ST regulated mitophagy signaling via inhibiting LC3-II and P62 levels and increasing PINK/Parkin expression. 15 min ST also inhibited ROS production and enhanced antioxidant SOD2 activity. Notably, 15 min ST significantly increased sirtuin (SIRT) 3 level (2.7-fold) in vivo while the inhibition of SIRT3 exacerbated senescent H9c2 cellular LDH release and ROS production under hypoxia. In addition, SIRT3 silencing impairs mitochondrial dynamics and mitophagy in senescent cardiomyocytes against simulated ischemia (SI) injury. Conclusion. Collectively, our study demonstrated for the first time that sustained short-duration exercise, rather than long-duration exercise, attenuates cardiac dysfunction after MI in aged mice. It is likely that the positive regulation induced by a short-duration ST regimen on the elevated SIRT3 protein level improved mitochondrial quality control and decreased apoptosis and fibrosis contributed to the observed more resistant phenotype.

scholarly journals Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle

2013 ◽  
Vol 115 (10) ◽  
pp. 1562-1571 ◽  
Author(s):  
Martin Picard ◽  
Benoit J. Gentil ◽  
Meagan J. McManus ◽  
Kathryn White ◽  
Kyle St. Louis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Cells ◽  
Mitochondrial Membrane ◽  
Acute Exercise ◽  
Exercise Intervention ◽  
Cultured Cells ◽  
Mitochondrial Dynamics ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Membrane Interactions

A unique property of mitochondria in mammalian cells is their ability to physically interact and undergo dynamic events of fusion/fission that remodel their morphology and possibly their function. In cultured cells, metabolic perturbations similar to those incurred during exercise influence mitochondrial fusion and fission processes, but it is unknown whether exercise acutely alters mitochondrial morphology and/or membrane interactions in vivo. To study this question, we subjected mice to a 3-h voluntarily exercise intervention following their normal physical activity patterns, and quantified mitochondrial morphology and membrane interactions in the soleus using a quantitative electron microscopy approach. A single exercise bout effectively decreased blood glucose ( P < 0.05) and intramyocellular lipid content ( P < 0.01), indicating increased muscle metabolic demand. The number of mitochondria spanning Z-lines and proportion of electron-dense contact sites (EDCS) between adjacent mitochondrial membranes were increased immediately after exercise among both subsarcolemmal (+116%, P < 0.05) and intermyofibrillar mitochondria (+191%, P < 0.001), indicating increased physical interactions. Mitochondrial morphology, and abundance of the mitochondrial pro-fusion proteins Mfn2 and OPA1 were unchanged. Collectively, these results support the notion that mitochondrial membrane dynamics are actively remodelled in skeletal muscle, which may be regulated by contractile activity and the metabolic state. Future studies are required to understand the implications of mitochondrial dynamics in skeletal muscle physiology during exercise and inactivity.

scholarly journals The Role of Mitochondrial Quality Control in Cardiac Ischemia/Reperfusion Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jia Huang ◽  
Ruibing Li ◽  
Chengbin Wang
Keyword(s):  
Quality Control ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Mitochondrial Quality Control

A healthy mitochondrial network produces a large amount of ATP and biosynthetic intermediates to provide sufficient energy for myocardium and maintain normal cell metabolism. Mitochondria form a dynamic and interconnected network involved in various cellular metabolic signaling pathways. As mitochondria are damaged, controlling mitochondrial quantity and quality is activated by changing their morphology and tube network structure, mitophagy, and biogenesis to replenish a healthy mitochondrial network to preserve cell function. There is no doubt that mitochondrial dysfunction has become a key factor in many diseases. Ischemia/reperfusion (IR) injury is a pathological manifestation of various heart diseases. Cardiac ischemia causes temporary tissue and organelle damage. Although reperfusion is essential to compensate for nutrient deficiency, blood flow restoration inconsequently further kills the previously ischemic cardiomyocytes. To date, dysfunctional mitochondria and disturbed mitochondrial quality control have been identified as critical IR injury mechanisms. Many researchers have detected abnormal mitochondrial morphology and mitophagy, as well as aberrant levels and activity of mitochondrial biogenesis factors in the IR injury model. Although mitochondrial damage is well-known in myocardial IR injury, the causal relationship between abnormal mitochondrial quality control and IR injury has not been established. This review briefly describes the molecular mechanisms of mitochondrial quality control, summarizes our current understanding of the complex role of mitochondrial quality control in IR injury, and finally speculates on the possibility of targeted control of mitochondria and the methods available to mitigate IR injury.

scholarly journals The Interplay among PINK1/PARKIN/Dj-1 Network during Mitochondrial Quality Control in Cancer Biology: Protein Interaction Analysis

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 154 ◽  
Author(s):  
Celia Salazar ◽  
Paula Ruiz-Hincapie ◽  
Lina Ruiz
Keyword(s):  
Quality Control ◽  
Protein Interactions ◽  
Cancer Biology ◽  
Mitochondrial Membrane ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Mitochondrial Morphology ◽  
Transcriptional Level ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Quality Control

PARKIN (E3 ubiquitin ligase PARK2), PINK1 (PTEN induced kinase 1) and DJ-1 (PARK7) are proteins involved in autosomal recessive parkinsonism, and carcinogenic processes. In damaged mitochondria, PINK1’s importing into the inner mitochondrial membrane is prevented, PARKIN presents a partial mitochondrial localization at the outer mitochondrial membrane and DJ-1 relocates to mitochondria when oxidative stress increases. Depletion of these proteins result in abnormal mitochondrial morphology. PINK1, PARKIN, and DJ-1 participate in mitochondrial remodeling and actively regulate mitochondrial quality control. In this review, we highlight that PARKIN, PINK1, and DJ-1 should be regarded as having an important role in Cancer Biology. The STRING database and Gene Ontology (GO) enrichment analysis were performed to consolidate knowledge of well-known protein interactions for PINK1, PARKIN, and DJ-1 and envisage new ones. The enrichment analysis of KEGG pathways showed that the PINK1/PARKIN/DJ-1 network resulted in Parkinson disease as the main feature, while the protein DJ-1 showed enrichment in prostate cancer and p53 signaling pathway. Some predicted transcription factors regulating PINK1, PARK2 (PARKIN) and PARK7 (DJ-1) gene expression are related to cell cycle control. We can therefore suggest that the interplay among PINK1/PARKIN/DJ-1 network during mitochondrial quality control in cancer biology may occur at the transcriptional level. Further analysis, like a systems biology approach, will be helpful in the understanding of PINK1/PARKIN/DJ-1 network.

scholarly journals At the heart of mitochondrial quality control: many roads to the top

2021 ◽  
Author(s):  
Roberta A. Gottlieb ◽  
Honit Piplani ◽  
Jon Sin ◽  
Savannah Sawaged ◽  
Syed M. Hamid ◽  
...  
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Unfolded Protein ◽  
Selective Elimination ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

AbstractMitochondrial quality control depends upon selective elimination of damaged mitochondria, replacement by mitochondrial biogenesis, redistribution of mitochondrial components across the network by fusion, and segregation of damaged mitochondria by fission prior to mitophagy. In this review, we focus on mitochondrial dynamics (fusion/fission), mitophagy, and other mechanisms supporting mitochondrial quality control including maintenance of mtDNA and the mitochondrial unfolded protein response, particularly in the context of the heart.

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 Editorial: Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda Lochner ◽  
Hsueh-Hsiao Wang ◽  
Russel J. Reiter ◽  
Rui Guo ◽  
Hao Zhou
Keyword(s):  
Quality Control ◽  
Mitochondrial Quality Control
Sign in / Sign up

Export Citation Format

Share Document