Quantification of Mitochondrial Network Characteristics in Health and Disease

Author(s):  
Andrew J. Valente ◽  
Joao Fonseca ◽  
Fereshteh Moradi ◽  
Gregory Foran ◽  
Alexander Necakov ◽  
...  
Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 157 ◽  
Author(s):  
Joao Fonseca ◽  
Fereshteh Moradi ◽  
Andrew Valente ◽  
Jeffrey Stuart

Resveratrol is a plant-derived polyphenol that has been widely studied for its putative health promoting effects. Many of those studies have been conducted in cell culture, in supra-physiological levels of oxygen and glucose. Resveratrol interacts with reactive oxygen species (ROS) as an antioxidant or pro-oxidant. Resveratrol affects the expression and activities of ROS-producing enzymes and organelles. It is therefore important to consider how cell culture conditions might determine the effects of resveratrol on cultured cells. We determined the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics in C2C12 mouse myoblasts and PC3 human prostate cancer cells under conditions of physiological (5%) and supra-physiological (18%) oxygen, and normo- (5 mM) and hyper-glycemia (25 mM). Interestingly, most effects of resveratrol on the parameters measured here were dependent upon prevailing oxygen and glucose levels during the experiment. Many of the effects of resveratrol on cell growth, hydrogen peroxide production, and mitochondrial network characteristics that were seen in 25 mM glucose and/or 18% oxygen were absent under the physiologically relevant conditions of 5 mM glucose with 5% oxygen. These findings emphasize the importance of using physiologically meaningful starting conditions for cell-culture experiments with resveratrol and indeed any manipulation affecting ROS metabolism and mitochondria.


2016 ◽  
Vol 130 (15) ◽  
pp. 1285-1305 ◽  
Author(s):  
Miguel A. Aon ◽  
Sonia Cortassa ◽  
Magdalena Juhaszova ◽  
Steven J. Sollott

Food nutrients and metabolic supply–demand dynamics constitute environmental factors that interact with our genome influencing health and disease states. These gene–environment interactions converge at the metabolic–epigenome–genome axis to regulate gene expression and phenotypic outcomes. Mounting evidence indicates that nutrients and lifestyle strongly influence genome–metabolic functional interactions determining disease via altered epigenetic regulation. The mitochondrial network is a central player of the metabolic–epigenome–genome axis, regulating the level of key metabolites [NAD+, AcCoA (acetyl CoA), ATP] acting as substrates/cofactors for acetyl transferases, kinases (e.g. protein kinase A) and deacetylases (e.g. sirtuins, SIRTs). The chromatin, an assembly of DNA and nucleoproteins, regulates the transcriptional process, acting at the epigenomic interface between metabolism and the genome. Within this framework, we review existing evidence showing that preservation of mitochondrial network function is directly involved in decreasing the rate of damage accumulation thus slowing aging and improving healthspan.


2020 ◽  
Vol 219 (11) ◽  
Author(s):  
Samuel A. Killackey ◽  
Dana J. Philpott ◽  
Stephen E. Girardin

Mitophagy is an evolutionarily conserved process involving the autophagic targeting and clearance of mitochondria destined for removal. Recent insights into the complex nature of the overlapping pathways regulating mitophagy illustrate mitophagy’s essential role in maintaining the health of the mitochondrial network. In this review, we highlight recent studies that have changed the way mitophagy is understood, from initiation through lysosomal degradation. We outline the numerous mitophagic receptors and triggers, with a focus on basal and physiologically relevant cues, offering insight into why they lead to mitochondrial removal. We also explore how mitophagy maintains mitochondrial homeostasis at the organ and system levels and how a loss of mitophagy may play a role in a diverse group of diseases, including cardiovascular, metabolic, and neurodegenerative diseases. With disrupted mitophagy affecting such a wide array of physiological processes, a deeper understanding of how to modulate mitophagy could provide avenues for numerous therapies.


Author(s):  
Sarah A. Luse

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.


2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.


1965 ◽  
Vol 48 (6) ◽  
pp. 758-767 ◽  
Author(s):  
Lansing C. Hoskins ◽  
Norman Zamcheck

1959 ◽  
Vol 36 (2) ◽  
pp. 193-201 ◽  
Author(s):  
Julius A. Goldbarg ◽  
Esteban P. Pineda ◽  
Benjamin M. Banks ◽  
Alexander M. Rutenburg

1973 ◽  
Vol 131 (6) ◽  
pp. 901-904 ◽  
Author(s):  
N. A. Kurtzman

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