Understanding Of Mitochondria Research Articles

Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle.

Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency. We determined the free Ca2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction-diffusion Ca2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export. [Ca2+]mito during tetanic stimulation is greater in knock-out (KO) (1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non-linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/Lfiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/Lfiber, ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store-operated calcium entry in KO compared to WT. However, levels of [Ca2+]cyto during tetanic stimulation were not modulated to variations of extracellular calcium. The model-based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers.

Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)−1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.

A Workshop on Mitochondria for Students to Improve Understanding of Science and Hypothesis Forming.

There remains a clear deficiency in recruiting middle school students in science, technology, engineering, mathematics, and medicine (STEMM) fields, especially for those students entering physiology from underrepresented backgrounds. A large part of this may be arising from a disconnect between how science is typically practiced at a collegiate and K-12 level. Here, we have envisioned mitochondria and their diverse subcellular structures as an involver for middle school, high school, and undergraduate students. We present the framework for a workshop that familiarizes students with mitochondria, employing 3D visual-spatial learning and real-time critical thinking and hypothesis forming. This workshop had the goal of familiarizing middle school students with the unique challenges the field currently faces, and better understanding the actuality of being a scientist through critical analysis including hypothesis forming. Findings show that as tested with middle school students responded positively to the program and felt as though they had a better understanding of mitochondria. Future implications for hands-on programs to involve underrepresented students in science are discussed.

Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis.

Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes. To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied. In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive. This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.

Mitochondrial Control of Stem Cell State and Fate: Lessons From Drosophila.

Over the years, Drosophila has served as a wonderful genetically tractable model system to unravel various facets of tissue-resident stem cells in their microenvironment. Studies in different stem and progenitor cell types of Drosophila have led to the discovery of cell-intrinsic and extrinsic factors crucial for stem cell state and fate. Though initially touted as the ATP generating machines for carrying various cellular processes, it is now increasingly becoming clear that mitochondrial processes alone can override the cellular program of stem cells. The last few years have witnessed a surge in our understanding of mitochondria’s contribution to governing different stem cell properties in their subtissular niches in Drosophila. Through this review, we intend to sum up and highlight the outcome of these in vivo studies that implicate mitochondria as a central regulator of stem cell fate decisions; to find the commonalities and uniqueness associated with these regulatory mechanisms.

Mitochondria in Health and Disease – 3rd Annual Conference of Society for Mitochondrial Research and Medicine – 19–20 December 2013 — Bengaluru, India

The primary role of mitochondria was long considered to be production of cellular energy. However, as the understanding of mitochondria in disease is ever expanding, so is their additional function for a healthy organism. Mitochondrial dysfunction is linked to a range of pathologies, including cancer, neurodegenerative disorders, premature aging, diabetes and muscular diseases. Mitochondrial diseases can be hard to diagnose and treat and, therefore, interdisciplinary research and communication are important. The Third Annual Conference of Society for Mitochondrial Research and Medicine — India (SMRM) was titled “Mitochondria in Health and Disease”. The conference was organized by Gayathri N, K Thangaraj, and KK Singh and was held at the National Institute of Mental Health & Neuro Sciences (NIMHANS) in Bangalore, India, from the 19th to 20th of December 2013. The meeting featured internationally renowned speakers within the field of mitochondrial research and medicine with the goal of bridging the gap between basic and clinical researchers. This review summarizes key outcomes of the conference.

Energy metabolism among eukaryotic anaerobes in light of Proterozoic ocean chemistry.

Recent years have witnessed major upheavals in views about early eukaryotic evolution. One very significant finding was that mitochondria, including hydrogenosomes and the newly discovered mitosomes, are just as ubiquitous and defining among eukaryotes as the nucleus itself. A second important advance concerns the readjustment, still in progress, about phylogenetic relationships among eukaryotic groups and the roughly six new eukaryotic supergroups that are currently at the focus of much attention. From the standpoint of energy metabolism (the biochemical means through which eukaryotes gain their ATP, thereby enabling any and all evolution of other traits), understanding of mitochondria among eukaryotic anaerobes has improved. The mainstream formulations of endosymbiotic theory did not predict the ubiquity of mitochondria among anaerobic eukaryotes, while an alternative hypothesis that specifically addressed the evolutionary origin of energy metabolism among eukaryotic anaerobes did. Those developments in biology have been paralleled by a similar upheaval in the Earth sciences regarding views about the prevalence of oxygen in the oceans during the Proterozoic (the time from ca 2.5 to 0.6 Ga ago). The new model of Proterozoic ocean chemistry indicates that the oceans were anoxic and sulphidic during most of the Proterozoic. Its proponents suggest the underlying geochemical mechanism to entail the weathering of continental sulphides by atmospheric oxygen to sulphate, which was carried into the oceans as sulphate, fueling marine sulphate reducers (anaerobic, hydrogen sulphide-producing prokaryotes) on a global scale. Taken together, these two mutually compatible developments in biology and geology underscore the evolutionary significance of oxygen-independent ATP-generating pathways in mitochondria, including those of various metazoan groups, as a watermark of the environments within which eukaryotes arose and diversified into their major lineages.

A hyperstructure approach to mitochondria.

Several questions in our understanding of mitochondria are unanswered. These include how the ratio of mitochondrial (mt)DNA to mitochondria is maintained, how the accumulation of defective, rapidly replicating mitochondrial DNA is avoided, how the ratio of mitochondria to cells is adjusted to fit cellular needs, and why any proteins are synthesized in mitochondria rather than simply imported. In bacteria, large hyperstructures or assemblies of proteins, mRNA, lipids and ions have been proposed to constitute a level of organization intermediate between macromolecules and whole cells. Here, we suggest how the concept of hyperstructures together with other concepts developed for bacteria such as transcriptional sensing and spontaneous segregation may provide answers to mitochondrial problems. In doing this, we show how the problem of the very existence of mtDNA brings its own solution.