scholarly journals Cardiolipin, Non-Bilayer Structures and Mitochondrial Bioenergetics: Relevance to Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1721
Author(s):  
Edward S. Gasanoff ◽  
Lev S. Yaguzhinsky ◽  
Győző Garab
Keyword(s):  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Mitochondrial Bioenergetics ◽  
Mitochondrial Membranes ◽  
Inner Mitochondrial Membrane ◽  
Atp Production ◽  
Functional Roles ◽  
Transport Chain ◽  
Energy Converting

The present review is an attempt to conceptualize a contemporary understanding about the roles that cardiolipin, a mitochondrial specific conical phospholipid, and non-bilayer structures, predominantly found in the inner mitochondrial membrane (IMM), play in mitochondrial bioenergetics. This review outlines the link between changes in mitochondrial cardiolipin concentration and changes in mitochondrial bioenergetics, including changes in the IMM curvature and surface area, cristae density and architecture, efficiency of electron transport chain (ETC), interaction of ETC proteins, oligomerization of respiratory complexes, and mitochondrial ATP production. A relationship between cardiolipin decline in IMM and mitochondrial dysfunction leading to various diseases, including cardiovascular diseases, is thoroughly presented. Particular attention is paid to the targeting of cardiolipin by Szeto–Schiller tetrapeptides, which leads to rejuvenation of important mitochondrial activities in dysfunctional and aging mitochondria. The role of cardiolipin in triggering non-bilayer structures and the functional roles of non-bilayer structures in energy-converting membranes are reviewed. The latest studies on non-bilayer structures induced by cobra venom peptides are examined in model and mitochondrial membranes, including studies on how non-bilayer structures modulate mitochondrial activities. A mechanism by which non-bilayer compartments are formed in the apex of cristae and by which non-bilayer compartments facilitate ATP synthase dimerization and ATP production is also presented.

Study of the anti-angiogenic effects of cardiolipin by the aortic ring assay

2015 ◽  
Vol 93 (11) ◽  
pp. 1015-1019 ◽  
Author(s):  
Matthew L. Carnevale ◽  
Andreas Bergdahl
Keyword(s):  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Aortic Ring ◽  
Cell Types ◽  
Inner Mitochondrial Membrane ◽  
Transport Chain ◽  
Aortic Ring Assay ◽  
Cervical Dislocation ◽  
Sprout Growth

Cardiolipin (CL), a phospholipid found in the inner mitochondrial membrane in all cell types, is critical for the function of the electron transport chain. The role of CL is not fully understood, but it is assumed that the molecule maintains membrane potential and architecture and compensates for alterations in homeostasis that could affect the energy metabolism. The objective of this project was to determine the effects of increasing CL concentrations on angiogenic sprouting by using the aortic ring assay model. For this, 5-day-old C57Bl/6 pups were euthanized by cervical dislocation prior to removal of the aortas. The vessels were cleaned, cut in 0.5 mm wide rings, and placed in a collagen growth matrix supplemented with CL. The results revealed a highly significant reduction of sprout growth (both length and quantity) at low, physiological concentrations. In conclusion, the results of this study demonstrate that CL significantly reduces microvessel formation and that it could potentially provide an interesting novel therapeutic target for angiogenesis.

scholarly journals Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 728 ◽  
Author(s):  
Giuseppe Paradies ◽  
Valeria Paradies ◽  
Francesca M. Ruggiero ◽  
Giuseppe Petrosillo
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Protein Import ◽  
Building Blocks ◽  
Inner Mitochondrial Membrane ◽  
Atp Production ◽  
Membrane Morphology ◽  
Transport Chain ◽  
Health And Disease

In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.

Mitochondrial ion circuits

2010 ◽  
Vol 47 ◽  
pp. 25-35 ◽  
Author(s):  
David G. Nicholls
Keyword(s):  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Primary Energy ◽  
Proton Leak ◽  
Primary Proton ◽  
Inner Mitochondrial Membrane ◽  
Intact Cells ◽  
Transport Chain ◽  
Proton Current ◽  
Circuit Techniques

Proton circuits across the inner mitochondrial membrane link the primary energy generators, namely the complexes of the electron transport chain, to multiple energy utilizing processes, including the ATP synthase, inherent proton leak pathways, metabolite transport and linked circuits of sodium and calcium. These mitochondrial circuits can be monitored in both isolated preparations and intact cells and, for the primary proton circuit techniques, exist to follow both the proton current and proton electrochemical potential components of the circuit in parallel experiments, providing a quantitative means of assessing mitochondrial function and, equally importantly, dysfunction.

scholarly journals Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants

2021 ◽  
Author(s):  
Alisha G. Lewis ◽  
Robert Caldwell ◽  
Jason V. Rogers ◽  
Maria Ingaramo ◽  
Rebecca Y. Wang ◽  
...  
Keyword(s):  
Electron Transport ◽  
Signaling Pathways ◽  
Electron Transport Chain ◽  
Nutrient Sensing ◽  
Ph Homeostasis ◽  
Inner Mitochondrial Membrane ◽  
Age Related ◽  
Transport Chain ◽  
Major Nutrient

The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear if these phenotypes directly cause the suppression or are simply effects. This work further highlights the complex cellular network connections between metabolic pathways and signaling events in the cell, and their potential roles in aging and age-related diseases.

scholarly journals Mitochondria-targeted molecules determine the redness of the zebra finch bill

2017 ◽  
Vol 13 (10) ◽  
pp. 20170455 ◽  
Author(s):  
Alejandro Cantarero ◽  
Carlos Alonso-Alvarez
Keyword(s):  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Coenzyme Q ◽  
Antioxidant Properties ◽  
Quality Indices ◽  
Inner Mitochondrial Membrane ◽  
Animal Cells ◽  
Transport Chain ◽  
Sexual Signalling ◽  
Production Mechanisms

The evolution and production mechanisms of red carotenoid-based ornaments in animals are poorly understood. Recently, it has been suggested that enzymes transforming yellow carotenoids to red pigments (ketolases) in animal cells may be positioned in the inner mitochondrial membrane (IMM) intimately linked to the electron transport chain. These enzymes may mostly synthesize coenzyme Q 10 (coQ 10 ), a key redox-cycler antioxidant molecularly similar to yellow carotenoids. It has been hypothesized that this shared pathway favours the evolution of red traits as sexually selected individual quality indices by revealing a well-adjusted oxidative metabolism. We administered mitochondria-targeted molecules to male zebra finches ( Taeniopygia guttata ) measuring their bill redness, a trait produced by transforming yellow carotenoids. One molecule included coQ 10 (mitoquinone mesylate, MitoQ) and the other one (decyl-triphenylphosphonium; dTPP) has the same structure without the coQ 10 aromatic ring. At the highest dose, the bill colour of MitoQ and dTPP birds strongly differed: MitoQ birds' bills were redder and dTPP birds showed paler bills even compared to birds injected with saline only. These results suggest that ketolases are indeed placed at the IMM and that coQ 10 antioxidant properties may improve their efficiency. The implications for evolutionary theories of sexual signalling are discussed.

scholarly journals Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

2021 ◽  
Vol 8 ◽  
Author(s):  
Domenico Sergi ◽  
Natalie Luscombe-Marsh ◽  
Nenad Naumovski ◽  
Mahinda Abeywardena ◽  
Nathan O'Callaghan
Keyword(s):  
Insulin Resistance ◽  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Chain Complex ◽  
Mitochondrial Fragmentation ◽  
Metabolic Inflammation ◽  
Transport Chain

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

Mitochondrial Dysfunction in Aging and Neurodegeneration

2019 ◽  
pp. 76-101
Author(s):  
Vaibhav Walia ◽  
Munish Garg
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Electron Transport Chain ◽  
Tricarboxylic Acid ◽  
Atp Production ◽  
Important Target ◽  
Transport Chain ◽  
Cellular Apoptosis

Mitochondria are a dynamic organelle of the cell involved in the various biological processes. Mitochondria are the site of the adenosine triphosphate (ATP) production, electron transport chain (ETC), oxidation of fatty acids, tricarboxylic acid (TCA), and cellular apoptosis. Besides these, mitochondria are the site of production of reactive oxygen species (ROS), which further disrupts the normal functioning of this organelle also making mitochondria itself as an important target of oxidative stress. Thus, mitochondria serve as an important target in the process of neurodegeneration. In the present chapter, the authors describe mitochondria and its functioning, dynamics, and the mitochondrial dysfunction in aging and neurodegenerative disorders (NDs).

scholarly journals An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

2005 ◽  
Vol 77 (4) ◽  
pp. 695-715 ◽  
Author(s):  
Michele A. Zacks ◽  
Jian-Jun Wen ◽  
Galina Vyatkina ◽  
Vandanajay Bhatia ◽  
Nisha Garg
Keyword(s):  
Oxidative Stress ◽  
Electron Transport Chain ◽  
Common Source ◽  
Oxygen Species ◽  
Pathogen Invasion ◽  
Immune Mediated ◽  
Transport Chain ◽  
Chagasic Cardiomyopathy ◽  
The Common

There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stress-induced injuries that may contribute to disease progression. Pathogen invasion- and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.

The Electron Transport Chain

2014 ◽  
Vol 76 (7) ◽  
pp. 456-458 ◽  
Author(s):  
Chris Romero ◽  
James Choun
Keyword(s):  
Electron Transport ◽  
Advanced Placement ◽  
Electron Transport Chain ◽  
Cellular Respiration ◽  
College Level ◽  
Inner Mitochondrial Membrane ◽  
College Biology ◽  
Everyday Objects ◽  
Transport Chain ◽  
Introductory College

This activity provides students an interactive demonstration of the electron transport chain and chemiosmosis during aerobic respiration. Students use simple, everyday objects as hydrogen ions and electrons and play the roles of the various proteins embedded in the inner mitochondrial membrane to show how this specific process in cellular respiration produces ATP. The activity works best as a supplement after you have already discussed the electron transport chain in lecture but can be used prior to instruction to help students visualize the processes that occur. This demonstration was designed for general college biology for majors at a community college, but it could be used in any introductory college-level or advanced placement biology course.

Sign in / Sign up

Export Citation Format

Share Document