Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Regulation of skeletal muscle mitochondria in response to obesity and exercise in mice and humans

Skeletal muscle mitochondria are highly plastic organelles, integral to whole-body health. High-fat diet (HFD) and exercise remodel the skeletal muscle mitochondria. Whereby, altered skeletal muscle mitochondrial function is linked to decreased skeletal muscle insulin sensitivity which can be reversed by exercise. However, the mechanisms that contribute to skeletal muscle remodeling in response to high-fat diet induced obesity, and exercise remain to be completely elucidated. The overall aim of this dissertation was to investigate the remodeling of skeletal mitochondria as a mechanism underlying respiratory function. The primary mechanisms of focus were the remodeling of skeletal muscle electron transferring flavoprotein (ETF) in female mice; the remodeling of skeletal muscle transcriptome and induction of autophagy in response to high-intensity interval training, in lean sedentary humans; and the underlying transcriptional patterns predictive of mitochondrial respiration in sedentary humans. Exercise increases skeletal muscle mitochondrial lipid metabolism which may be mediated through stimulation of synthesis of ETF proteins. However, compared to males, female mice tend to have greater mitochondrial abundance and lipid respiration that may limit the adaptive response. Therefore, we determined mitochondrial remodeling for lipid respiration through ETF in the context of higher mitochondrial abundance/capacity seen in female mice. Female mice consumed HFD, or low-fat diet (LFD) for 4 weeks then remained sedentary (SED) or completed 8 weeks of treadmill training (EX). HFD increased absolute and relative lipid respiration capacity and RNA abundance for ETF, ETF, and ETFDH. HFD increased synthesis for ETF and ETFDH. EX increased synthesis of ETF and ETFDH. Higher synthesis rates of ETF were not always reflected in greater protein abundance. Greater synthesis of ETF during HFD indicates mitochondrial remodeling which may contribute to increases to mitochondrial lipid respiration through enhanced ETF quality. Longer aerobic training (6 weeks) increases mitochondrial protein abundance and respiration through mechanisms including increased mitochondrial protein synthesis and lowered oxidative damage. Such changes indicate training can increase mitochondrial abundance and quality over time. The short-term impact of training on abundance versus quality is less clear. Time-course studies demonstrate several sessions of exercise increase the abundance of transcription factors and proteins for mitochondria. Even a single session of exercise increases mitochondrial enzyme activity and respiration with negligible changes to mitochondrial protein abundance. Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms responsible for increases to mitochondrial respiration during initial training adaptations. Therefore, we determined changes to mitochondrial respiration and regulatory pathways that occur in response to short-term high-intensity interval training (HIIT). HIIT increased respiration per mitochondrial protein for lipid, complex I, complex I+II, and complex II. 48 hours after the final HIIT bout gene sets of mitochondrial respiration, particularly for complex I were upregulated, while pathways of DNA and chromatin remodeling were downregulated. We tested the degradation of mitochondria as a mechanism for remodeling and determined lower abundance in proteins that are cleared through autophagy (p62 and LC3II) which indicate activation of degradation after 2 weeks of HIIT. The lower abundance occurred at the whole tissue level but not isolated mitochondria, indicating that degradation was widespread across cell components. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation. Skeletal muscle mitochondrial respiratory capacity is associated with whole-body health and endurance performance capacity. However, the underlying transcriptional patterns that explain interindividual differences in mitochondrial respiratory capacity in sedentary individuals remain unknown. Therefore, we determined the association between gene abundance and mitochondrial respiration in a cohort of sedentary human adults. We measured mitochondrial respiratory capacity for four distinct states (lipid, complex I, complex I & II, and complex II) and gene transcripts using RNA-sequencing We found that higher mitochondrial respiratory capacity to oxidize lipids was positively associated with higher abundance of translational pathways including ribosome, translational initiation, and elongation, and negatively associated with mitochondrial gene pathways including fatty acid oxidation, and TCA cycle indicating greater influence from translational control for lipid respiration. Furthermore, specific respiratory states did not have overlapping gene associations. Taken together, this data provides evidence that unique transcriptomic fingerprints are associated with different mitochondrial respiratory states. The regulation of mitochondrial respiration occurs at the transcript, protein, and functional levels in response to high-fat diet, exercise, and in response to sedentary behavior. Altered skeletal muscle mitochondrial lipid metabolism observed with diet-induced obesity and/or aerobic exercise training is accompanied by remodeling of the electron-transferring flavoproteins which are important for the adaptative response of lipid respiration in female mice. The early adaptative response to exercise on skeletal muscle mitochondrial respiratory capacity are likely dependent on induction of remodeling pathways including activation of whole-cell degradation pathways and increased mRNA of gene pathways related to complex I, mitochondrial electron transfer capacity, and translational control that result in higher protein quality which precede changes to mitochondrial protein abundance. Lastly, unique skeletal muscle transcriptional patterns are predictive of distinct mitochondrial respiratory states in sedentary individuals at baseline. These observations further our understanding of regulation of skeletal muscle mitochondrial metabolism in response to various stresses. The adaptative response of the mitochondria to various environmental stresses remains an area ripe for future study

Pneumonia Diagnostic Device for Low-Resource Settings

Executive Summary of ME 450 F13 Team 10 Final Reporthttp://deepblue.lib.umich.edu/bitstream/2027.42/101971/1/ME450F13Project10__Summary.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/101971/2/ME450F13Project10__Photo.jp

Muscle oxygen saturation rates coincide with lactate-based exercise thresholds.

INTRODUCTION Monitoring muscle metabolic activity via blood lactate is a useful tool for understanding the physiological response to a given exercise intensity. Recent indications suggest that skeletal muscle oxygen saturation (SmO2), an index of the balance between local O2 supply and demand, may describe and predict endurance performance outcomes. PURPOSE We tested the hypothesis that SmO2 rate is tightly related to blood lactate concentration across exercise intensities, and that deflections in SmO2 rate would coincide with established blood lactate thresholds (i.e., lactate thresholds 1 and 2). METHODS Ten elite male soccer players completed an incremental running protocol to exhaustion using 3-min work to 30 s rest intervals. Blood lactate samples were collected during rest and SmO2 was collected continuously via near-infrared spectroscopy from the right and left vastus lateralis, left biceps femoris and the left gastrocnemius. RESULTS Muscle O2 saturation rate (%/min) was quantified after the initial 60 s of each 3-min segment. The SmO2 rate was significantly correlated with blood lactate concentrations for all muscle sites; RVL, r = - 0.974; LVL, r = - 0.969; LG, r = - 0.942; LHAM, r = - 0.907. Breakpoints in SmO2 rate were not significantly different from LT1 or LT2 at any muscle sites (P > 0.05). Bland-Altman analysis showed speed threshold estimates via SmO2 rate and lactate are similar at LT2, but slightly greater for SmO2 rate at LT1. CONCLUSIONS Muscle O2 saturation rate appears to provide actionable information about maximal metabolic steady state and is consistent with bioenergetic reliance on oxygen and its involvement in the attainment of metabolic steady state

High-intensity interval exercise reduces tolerance to a simulated haemorrhagic challenge in heat-stressed individuals

New FindingsWhat is the central question of this study? In heat-stressed individuals, does high-intensity interval exercise reduce tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) relative to steady state exercise?What is the main finding and its importance? LBNP tolerance was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. This was likely owing to the greater cardiovascular strain required to maintain arterial blood pressure prior to and early during LBNP following high-intensity interval exercise. These findings are of importance for individuals working in occupations in which combined heat stress and intense intermittent exercise are common and where the risk of haemorrhagic injury is increased.This study investigated whether tolerance to a simulated haemorrhagic challenge (lower body negative pressure, LBNP) was lower in heat-stressed individuals following high-intensity interval exercise relative to steady state exercise. Nine healthy participants completed two trials (Steady State and Interval). Participants cycled continuously at similar to 38% (Steady State) or alternating between 10 and similar to 88% (Interval) of the maximal power output whilst wearing a hot water perfused suit until core temperatures increased similar to 1.4 degrees C. Participants then underwent LBNP to pre-syncope. LBNP tolerance was quantified as cumulative stress index (CSI; mmHg min). Mean skin and core temperatures were elevated in both trials following exercise prior to LBNP (to 38.1 +/- 0.6 degrees C and 38.3 +/- 0.2 degrees C, respectively, both P 0.05). In the Interval trial, heart rate was greater (122 +/- 12 beats min(-1)) prior to LBNP, relative to the Steady State trial (107 +/- 8 beats min(-1), P < 0.001) while mean arterial pressure was similarly reduced in both trials prior to LBNP (from baseline 89 +/- 5 to 77 +/- 7 mmHg; P = 0.001) and at pre-syncope (to 62 +/- 9 mmHg, P < 0.001). CSI was lower in the Interval trial (280 +/- 194 vs. 550 +/- 234 mmHg min; P = 0.0085). In heat-stressed individuals, tolerance to a simulated haemorrhagic challenge is reduced following high-intensity interval exercise relative to steady state exercise