scholarly journals Targeting of the respiratory chain by toxicants: beyond the toxicities to mitochondrial morphology

2018 ◽  
Vol 7 (6) ◽  
pp. 1008-1011 ◽  
Author(s):  
P. K. Zhou ◽  
R. X. Huang
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Morphology ◽  
Environmental Toxicants ◽  
Subcellular Target

The mitochondrion is an important subcellular target of environmental toxicants.

Neither respiration nor cytochrome c oxidase affects mitochondrial morphology in Saccharomyces cerevisiae.

1998 ◽  
Vol 201 (11) ◽  
pp. 1729-1737 ◽  
Author(s):  
C Church ◽  
R O Poyton
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Glucose Repression ◽  
Nuclear Gene ◽  
Yeast Cells ◽  
Mitochondrial Proteins ◽  
Mitochondrial Morphology ◽  
Per Se ◽  
Mitochondrial Reticulum

Previous studies have reported that mitochondrial morphology and volume in yeast cells are linked to cellular respiratory capacity. These studies revealed that mitochondrial morphology in glucose-repressed or anaerobically grown cells, which lack or have reduced levels of respiration, is different from that in fully respiring cells. Although both oxygen deprivation and glucose repression decrease the levels of respiratory chain proteins, they decrease the expression of many non-mitochondrial proteins as well, making it difficult to determine whether it is a defect in respiration or something else that effects mitochondrial morphology. To determine whether mitochondrial morphology is dependent on respiration per se, we used a strain with a null mutation in PET100, a nuclear gene that is specifically required for the assembly of cytochrome c oxidase. Although this strain lacks respiration, the mitochondrial morphology and volumes are both comparable to those found in its respiration-proficient parent. These findings indicate that respiration is not involved in the establishment or maintenance of yeast mitochondrial morphology, and that the previously observed effects of oxygen availability and glucose repression on mitochondrial morphology are not exerted through the respiratory chain. By applying the principle of symmorphosis to these findings, we conclude that the shape and size of the mitochondrial reticulum found in respiring yeast cells is maintained for reasons other than respiration.

scholarly journals Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria

2016 ◽  
Vol 212 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Anne Korwitz ◽  
Carsten Merkwirth ◽  
Ricarda Richter-Dennerlein ◽  
Simon E. Tröder ◽  
Hans-Georg Sprenger ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Respiratory Chain ◽  
Neuronal Death ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Proteolytic Cleavage ◽  
Mitochondrial Morphology ◽  
Guanosine Triphosphatase

Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondrial morphology under stress and in disease. Stress-induced OPA1 processing by OMA1 triggersmitochondrial fragmentation, which is associated with mitophagy and apoptosis in vitro. Here, we identify OMA1 as a critical regulator of neuronal survival in vivo and demonstrate that stress-induced OPA1 processing by OMA1 promotes neuronal death and neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds as a model of neurodegeneration, we demonstrate that additional ablation of Oma1 delays neuronal loss and prolongs lifespan. This is accompanied by the accumulation of fusion-active, long OPA1 forms, which stabilize the mitochondrial genome but do not preserve mitochondrial cristae or respiratory chain supercomplex assembly in prohibitin-depleted neurons. Thus, long OPA1 forms can promote neuronal survival independently of cristae shape, whereas stress-induced OMA1 activation and OPA1 cleavage limit mitochondrial fusion and promote neuronal death.

Mitochondrial dysfunction: a key player in the pathogenesis of cardiovascular diseases linked to air pollution

2018 ◽  
Vol 33 (2) ◽  
pp. 111-122 ◽  
Author(s):  
Sri Rahavi Boovarahan ◽  
Gino A. Kurian
Keyword(s):  
Heart Failure ◽  
Air Pollution ◽  
Cardiovascular Diseases ◽  
Air Pollutants ◽  
Copy Number ◽  
Communicable Diseases ◽  
Mitochondrial Morphology ◽  
Cell Organelle ◽  
Environmental Toxicants ◽  
Non Communicable Diseases

Abstract Air pollution has become an environmental burden with regard to non-communicable diseases, particularly heart disease. It has been reported that air pollution can accelerate the development of heart failure and atrial fibrillation. Air pollutants encompass various particulate matters (PMs), which change the blood composition and heart rate and eventually leads to cardiac failure by triggering atherosclerotic plaque ruptures or by developing irreversible ischemia. A series of major epidemiological and observational studies have established the noxious effect of air pollutants on cardiovascular diseases (CVD), but the underlying molecular mechanisms of its susceptibility and the pathological disease events remain largely elusive and are predicted to be initiated in the cell organelle. The basis of this belief is that mitochondria are one of the major targets of environmental toxicants that can damage mitochondrial morphology, function and its DNA (manifested in non-communicable diseases). In this article, we review the literature related to air pollutants that adversely affect the progression of CVD and that target mitochondrial morphological and functional activities and how mitochondrial DNA (mtDNA) copy number variation, which reflects the airborne oxidant-induced cell damage, correlates with heart failure. We conclude that environmental health assessment should focus on the cellular/circulatory mitochondrial functional copy number status, which can predict the outcome of CVD.

scholarly journals Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion

2020 ◽  
pp. mbc.E20-09-0605
Author(s):  
Ruohan Wang ◽  
Prashant Mishra ◽  
Spiros D. Garbis ◽  
Annie Moradian ◽  
Michael J. Sweredoski ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Cleavage Site ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Cleavage Sites ◽  
Mrna Splice ◽  
Short Forms ◽  
Highly Sensitive ◽  
Dependent Site ◽  
Splice Forms

OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner-membrane-anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at cleavage sites S1 and S2 respectively, to produce short forms (s-OPA1). In both mouse and human, half of the mRNA splice forms of Opa1 are constitutively processed to yield exclusively s-OPA1. However, the function of s-OPA1 in mitochondrial fusion has been debated, because in some stress conditions, s-OPA1 is dispensable for fusion. By constructing cells in which the Opa1 locus no longer produces transcripts with S2 cleavage sites, we generated a simplified system to identify the new YME1L-dependent site S3 that mediates constitutive and complete cleavage of OPA1. We show that mitochondrial morphology is highly sensitive to the ratio of l-OPA1 to s-OPA1, indicating that s-OPA1 regulates mitochondrial fusion.

scholarly journals Selective and Reversible Disruption of Mitochondrial Inner Membrane Protein Complexes by Lipophilic Cations

2021 ◽  
Author(s):  
Anezka Kafkova ◽  
Lisa Tilokani ◽  
Filip Trčka ◽  
Veronika Šrámková ◽  
Marie Vancová ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Respiratory Chain ◽  
Mitochondrial Membrane ◽  
Mitochondrial Morphology ◽  
Respiratory Chain Complexes ◽  
Inner Membrane ◽  
Protein Levels ◽  
Mitochondrial Inner Membrane ◽  
Chain Complexes ◽  
The Impact

ABSTRACTMitochondria represent an attractive drug target in the treatment of many diseases. One of the most commonly used approaches to deliver therapeutics specifically into mitochondria is their conjugation to the triphenylphosphonium (TPP) moiety. While the TPP molecule is often regarded as biologically inert, there is evidence that the moiety itself has a significant impact on the activity of mitochondrial respiratory chain complexes.We studied the impact of a subchronic exposure of C2C12 mouse myoblasts to a set of TPP derivatives. Our results show that the alkyl-TPP cause dose- and hydrophobicity-dependent alterations of mitochondrial morphology and a selective decrease in the amounts of mitochondrial inner membrane (but not outer membrane) proteins including structural subunits of the respiratory chain complexes (such as MT-CO1 of complex IV or NDUFB8 of complex I), as well as components of the mitochondrial calcium uniporter complex (MCUC). The treatment with alkyl-TPP additionally resulted in OPA1-cleavage. Both the structural and functional effects of alkyl-TPP were found to be reversible. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ. We further show that this effect on protein levels cannot be explained solely by a decrease in mitochondrial membrane potential.We conclude that TPP derivatives negatively affect mitochondrial structure and function at least in part through their effect on selective mitochondrial membrane protein levels via a reversible controlled process.

Age-related changes in the activities of respiratory chain complexes and mitochondrial morphology in Drosophila

Mitochondrion ◽  
2012 ◽  
Vol 12 (2) ◽  
pp. 345-351 ◽  
Author(s):  
Yukiko Oda ◽  
Ryoko Yui ◽  
Kimitoshi Sakamoto ◽  
Kiyoshi Kita ◽  
Etsuko T. Matsuura
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Morphology ◽  
Respiratory Chain Complexes ◽  
Age Related ◽  
Chain Complexes ◽  
Age Related Changes
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