scholarly journals Evidence of Mitochondrial Dysfunction in Bacterial Chondronecrosis With Osteomyelitis–Affected Broilers

2021 ◽  
Vol 8 ◽  
Author(s):  
Alison Ferver ◽  
Elizabeth Greene ◽  
Robert Wideman ◽  
Sami Dridi
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Bacterial Infections ◽  
Mitochondrial Fission ◽  
Cellular Respiration ◽  
Mrna Levels ◽  
Mechanistic Investigation ◽  
Causative Agents ◽  
Dynamics And Function ◽  
And Function

A leading cause of lameness in modern broilers is bacterial chondronecrosis with osteomyelitis (BCO). While it is known that the components of BCO are bacterial infection, necrosis, and inflammation, the mechanism behind BCO etiology is not yet fully understood. In numerous species, including chicken, mitochondrial dysfunction has been shown to have a role in the pathogenicity of numerous diseases. The mitochondria is a known target for intracellular bacterial infections, similar to that of common causative agents in BCO, as well as a known regulator of cellular metabolism, stress response, and certain types of cell death. This study aimed to determine the expression profile of genes involved in mitochondrial biogenesis, dynamics, and function. RNA was isolated form the tibias from BCO-affected and healthy broilers and used to measure target gene expression via real-time qPCR. Mitochondrial biogenesis factors PGC-1α and PGC-1β were both significantly upregulated in BCO along with mitochondrial fission factors OMA1, MTFR1, MTFP1, and MFF1 as well as cellular respiration-related genes FOXO3, FOXO4, and av-UCP. Conversely, genes involved in mitochondrial function, ANT, COXIV, and COX5A showed decreased mRNA levels in BCO-affected tibia. This study is the first to provide evidence of potential mitochondrial dysfunction in BCO bone and warrants further mechanistic investigation into how this dysfunction contributes to BCO etiology.

scholarly journals Mitochondrial isolation: when size matters

2020 ◽  
Vol 5 ◽  
pp. 226
Author(s):  
Alexander G. Bury ◽  
Amy E. Vincent ◽  
Doug M. Turnbull ◽  
Paolo Actis ◽  
Gavin Hudson
Keyword(s):  
Mitochondrial Dysfunction ◽  
Single Cell ◽  
Cellular Heterogeneity ◽  
Single Cell Level ◽  
Cell Level ◽  
Isolation Techniques ◽  
Cellular Environment ◽  
Dynamics And Function ◽  
And Function ◽  
Subcellular Resolution

Mitochondrial vitality is critical to cellular function, with mitochondrial dysfunction linked to a growing number of human diseases. Tissue and cellular heterogeneity, in terms of genetics, dynamics and function means that increasingly mitochondrial research is conducted at the single cell level. Whilst, there are several single-cell technologies that are currently available, each with their advantages, they cannot be easily adapted to study mitochondria with subcellular resolution. Here we review the current techniques and strategies for mitochondrial isolation, critically discussing each technology’s limitations for future mitochondrial research. Finally, we highlight and discuss the recent breakthroughs in sub-cellular isolation techniques, with a particular focus on nanotechnologies that enable the isolation of mitochondria, from subcellular compartments, with unprecedented spatial precision with minimal disruption to mitochondria and their immediate cellular environment.

scholarly journals Placental Mitochondrial Abnormalities in Preeclampsia

2021 ◽  
Author(s):  
Philippe Vangrieken ◽  
Salwan Al-Nasiry ◽  
Aalt Bast ◽  
Pieter A. Leermakers ◽  
Christy B. M. Tulen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Expression Profiles ◽  
Mitochondrial Fission ◽  
Gene Expression Profiles ◽  
Molecular Pathways ◽  
Mrna Levels ◽  
Mitochondrial Content ◽  
Mitochondrial Abnormalities ◽  
Protein Levels

AbstractPreeclampsia complicates 5–8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis.

scholarly journals Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Chowdhury S. Abdullah ◽  
Richa Aishwarya ◽  
Shafiul Alam ◽  
Mahboob Morshed ◽  
Naznin Sultana Remex ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Illicit Drug ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Dynamics And Function ◽  
And Function

AbstractMethamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of “binge and crash” methamphetamine administration. Sigmar1 expression is significantly decreased in the hearts of human methamphetamine users and those of “binge and crash” methamphetamine-treated mice. The hearts of methamphetamine users also show signs of cardiomyopathy, including cellular injury, fibrosis, and enlargement of the heart. In addition, mice expose to “binge and crash” methamphetamine develop cardiac hypertrophy, fibrotic remodeling, and mitochondrial dysfunction leading to contractile dysfunction. Methamphetamine treatment inhibits Sigmar1, resulting in inactivation of the cAMP response element-binding protein (CREB), decreased expression of mitochondrial fission 1 protein (FIS1), and ultimately alteration of mitochondrial dynamics and function. Therefore, Sigmar1 is a viable therapeutic agent for protection against methamphetamine-associated cardiomyopathy.

scholarly journals Regulation of mitochondrial biogenesis

2010 ◽  
Vol 47 ◽  
pp. 69-84 ◽  
Author(s):  
François R. Jornayvaz ◽  
Gerald I. Shulman
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1 ◽  
And Function ◽  
Amp Activated Protein Kinase

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.

scholarly journals Hexestrol Deteriorates Oocyte Quality via Perturbation of Mitochondrial Dynamics and Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Dong Niu ◽  
Kun-Lin Chen ◽  
Yi Wang ◽  
Xiao-Qing Li ◽  
Lu Liu ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Oocyte Maturation ◽  
Ovarian Function ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Oocyte Quality ◽  
Early Embryo ◽  
Mitochondrial Distribution ◽  
Dynamics And Function ◽  
And Function

Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be transferred to humans from treated animals and the environment. HES has been shown to have an adverse effect on ovarian function and oogenesis, but the potential mechanism has not been clearly defined. To understand the potential mechanisms regarding how HES affect female ovarian function, we assessed oocyte quality by examining the critical events during oocyte maturation. We found that HES has an adverse effect on oocyte quality, indicated by the decreased capacity of oocyte maturation and early embryo development competency. Specifically, HES-exposed oocytes exhibited aberrant microtubule nucleation and spindle assembly, resulting in meiotic arrest. In addition, HES exposure disrupted mitochondrial distribution and the balance of mitochondrial fission and fusion, leading to aberrant mitochondrial membrane potential and accumulation of reactive oxygen species. Lastly, we found that HES exposure can increase cytosolic Ca2+ levels and induce DNA damage and early apoptosis. In summary, these results demonstrate that mitochondrial dysfunction and perturbation of normal mitochondrial fission and fusion dynamics could be major causes of reduced oocyte quality after HES exposure.

scholarly journals Mitochondrial dysfunction and consequences in calpain-3-deficient muscle

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vanessa E. Jahnke ◽  
Jennifer M. Peterson ◽  
Jack H. Van Der Meulen ◽  
Jessica Boehler ◽  
Kitipong Uaesoontrachoon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Mitochondrial Activity ◽  
Calpain 3 ◽  
And Function ◽  
Deficient Mice

Abstract Background Nonsense or loss-of-function mutations in the non-lysosomal cysteine protease calpain-3 result in limb-girdle muscular dystrophy type 2A (LGMD2A). While calpain-3 is implicated in muscle cell differentiation, sarcomere formation, and muscle cytoskeletal remodeling, the physiological basis for LGMD2A has remained elusive. Methods Cell growth, gene expression profiling, and mitochondrial content and function were analyzed using muscle and muscle cell cultures established from healthy and calpain-3-deficient mice. Calpain-3-deficient mice were also treated with PPAR-delta agonist (GW501516) to assess mitochondrial function and membrane repair. The unpaired t test was used to assess the significance of the differences observed between the two groups or treatments. ANOVAs were used to assess significance over time. Results We find that calpain-3 deficiency causes mitochondrial dysfunction in the muscles and myoblasts. Calpain-3-deficient myoblasts showed increased proliferation, and their gene expression profile showed aberrant mitochondrial biogenesis. Myotube gene expression analysis further revealed altered lipid metabolism in calpain-3-deficient muscle. Mitochondrial defects were validated in vitro and in vivo. We used GW501516 to improve mitochondrial biogenesis in vivo in 7-month-old calpain-3-deficient mice. This treatment improved satellite cell activity as indicated by increased MyoD and Pax7 mRNA expression. It also decreased muscle fatigability and reduced serum creatine kinase levels. The decreased mitochondrial function also impaired sarcolemmal repair in the calpain-3-deficient skeletal muscle. Improving mitochondrial activity by acute pyruvate treatment improved sarcolemmal repair. Conclusion Our results provide evidence that calpain-3 deficiency in the skeletal muscle is associated with poor mitochondrial biogenesis and function resulting in poor sarcolemmal repair. Addressing this deficit by drugs that improve mitochondrial activity offers new therapeutic avenues for LGMD2A.

scholarly journals Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 195 ◽  
Author(s):  
Bong Jhun ◽  
Jin O-Uchi ◽  
Stephanie Adaniya ◽  
Michael Cypress ◽  
Yisang Yoon
Keyword(s):  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Mitochondrial Fission ◽  
Ros Generation ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Signaling Activation ◽  
And Function

Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca2+ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF.

scholarly journals Growth Factor erv1-like Modulates Drp1 to Preserve Mitochondrial Dynamics and Function in Mouse Embryonic Stem Cells

2010 ◽  
Vol 21 (7) ◽  
pp. 1225-1236 ◽  
Author(s):  
Lance R. Todd ◽  
Matthew N. Damin ◽  
Rohini Gomathinayagam ◽  
Sarah R. Horn ◽  
Anthony R. Means ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Embryonic Stem ◽  
Pluripotency Marker ◽  
Marker Expression ◽  
Dynamics And Function ◽  
And Function

The relationship of mitochondrial dynamics and function to pluripotency are rather poorly understood aspects of stem cell biology. Here we show that growth factor erv1-like (Gfer) is involved in preserving mouse embryonic stem cell (ESC) mitochondrial morphology and function. Knockdown (KD) of Gfer in ESCs leads to decreased pluripotency marker expression, embryoid body (EB) formation, cell survival, and loss of mitochondrial function. Mitochondria in Gfer-KD ESCs undergo excessive fragmentation and mitophagy, whereas those in ESCs overexpressing Gfer appear elongated. Levels of the mitochondrial fission GTPase dynamin-related protein 1 (Drp1) are highly elevated in Gfer-KD ESCs and decreased in Gfer-overexpressing cells. Treatment with a specific inhibitor of Drp1 rescues mitochondrial function and apoptosis, whereas expression of Drp1-dominant negative resulted in the restoration of pluripotency marker expression in Gfer-KD ESCs. Altogether, our data reveal a novel prosurvival role for Gfer in maintaining mitochondrial fission–fusion dynamics in pluripotent ESCs.

Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure

2015 ◽  
Vol 309 (3) ◽  
pp. H434-H449 ◽  
Author(s):  
Knut H. Lauritzen ◽  
Liv Kleppa ◽  
Jan Magnus Aronsen ◽  
Lars Eide ◽  
Harald Carlsen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Fission ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Specific Expression ◽  
Mitochondrial Homeostasis ◽  
Transport Chain ◽  
Mtdna Replication ◽  
Dynamics And Function ◽  
And Function

Cardiac mitochondrial dysfunction has been implicated in heart failure of diverse etiologies. Generalized mitochondrial disease also leads to cardiomyopathy with various clinical manifestations. Impaired mitochondrial homeostasis may over time, such as in the aging heart, lead to cardiac dysfunction. Mitochondrial DNA (mtDNA), close to the electron transport chain and unprotected by histones, may be a primary pathogenetic site, but this is not known. Here, we test the hypothesis that cumulative damage of cardiomyocyte mtDNA leads to cardiomyopathy and heart failure. Transgenic mice with Tet-on inducible, cardiomyocyte-specific expression of a mutant uracil-DNA glycosylase 1 (mutUNG1) were generated. The mutUNG1 is known to remove thymine in addition to uracil from the mitochondrial genome, generating apyrimidinic sites, which obstruct mtDNA function. Following induction of mutUNG1 in cardiac myocytes by administering doxycycline, the mice developed hypertrophic cardiomyopathy, leading to congestive heart failure and premature death after ∼2 mo. The heart showed reduced mtDNA replication, severely diminished mtDNA transcription, and suppressed mitochondrial respiration with increased Pgc-1α, mitochondrial mass, and antioxidative defense enzymes, and finally failing mitochondrial fission/fusion dynamics and deteriorating myocardial contractility as the mechanism of heart failure. The approach provides a model with induced cardiac-restricted mtDNA damage for investigation of mtDNA-based heart disease.

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