-
Cell Research Sep 2023The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this...
The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this interaction in normal and failing hearts remains unknown. Lactate is a crucial energy substrate of the heart. Here, we identify that α-MHC undergoes lactylation on lysine 1897 to regulate the interaction of α-MHC with Titin. We observed a reduction of α-MHC K1897 lactylation in mice and patients with heart failure. Loss of K1897 lactylation in α-MHC K1897R knock-in mice reduces α-MHC-Titin interaction and leads to impaired cardiac structure and function. Furthermore, we identified that p300 and Sirtuin 1 act as the acyltransferase and delactylase of α-MHC, respectively. Decreasing lactate production by chemical or genetic manipulation reduces α-MHC lactylation, impairs α-MHC-Titin interaction and worsens heart failure. By contrast, upregulation of the lactate concentration by administering sodium lactate or inhibiting the pivotal lactate transporter in cardiomyocytes can promote α-MHC K1897 lactylation and α-MHC-Titin interaction, thereby alleviating heart failure. In conclusion, α-MHC lactylation is dynamically regulated and an important determinant of overall cardiac structure and function. Excessive lactate efflux and consumption by cardiomyocytes may decrease the intracellular lactate level, which is the main cause of reduced α-MHC K1897 lactylation during myocardial injury. Our study reveals that cardiac metabolism directly modulates the sarcomeric structure and function through lactate-dependent modification of α-MHC.
Topics: Animals; Mice; Connectin; Myosin Heavy Chains; Heart Failure; Myocytes, Cardiac; Lactates
PubMed: 37443257
DOI: 10.1038/s41422-023-00844-w -
Medicine and Science in Sports and... Oct 2023Protein ingestion during recovery from exercise has been reported to augment myofibrillar protein synthesis rates, without increasing muscle connective protein synthesis... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Protein ingestion during recovery from exercise has been reported to augment myofibrillar protein synthesis rates, without increasing muscle connective protein synthesis rates. It has been suggested that collagen protein may be effective in stimulating muscle connective protein synthesis. The present study assessed the capacity of both whey and collagen protein ingestion to stimulate postexercise myofibrillar and muscle connective protein synthesis rates.
METHODS
In a randomized, double-blind, parallel design, 45 young male ( n = 30) and female ( n = 15) recreational athletes (age, 25 ± 4 yr; body mass index, 24.1 ± 2.0 kg·m -2 ) were selected to receive primed continuous intravenous infusions with l -[ring- 13 C 6 ]-phenylalanine and l -[3,5- 2 H 2 ]-tyrosine. After a single session of resistance type exercise, subjects were randomly allocated to one of three groups ingesting either 30 g whey protein (WHEY, n = 15), 30 g collagen protein (COLL, n = 15) or a noncaloric placebo (PLA, n = 15). Blood and muscle biopsy samples were collected over a subsequent 5-h recovery period to assess both myofibrillar and muscle connective protein synthesis rates.
RESULTS
Protein ingestion increased circulating plasma amino acid concentrations ( P < 0.05). The postprandial rise in plasma leucine and essential amino acid concentrations was greater in WHEY compared with COLL, whereas plasma glycine and proline concentrations increased more in COLL compared with WHEY ( P < 0.05). Myofibrillar protein synthesis rates averaged 0.041 ± 0.010, 0.036 ± 0.010, and 0.032 ± 0.007%·h -1 in WHEY, COLL and PLA, respectively, with only WHEY resulting in higher rates when compared with PLA ( P < 0.05). Muscle connective protein synthesis rates averaged 0.072 ± 0.019, 0.068 ± 0.017, and 0.058 ± 0.018%·h -1 in WHEY, COLL, and PLA, respectively, with no significant differences between groups ( P = 0.09).
CONCLUSIONS
Ingestion of whey protein during recovery from exercise increases myofibrillar protein synthesis rates. Neither collagen nor whey protein ingestion further increased muscle connective protein synthesis rates during the early stages of postexercise recovery in both male and female recreational athletes.
Topics: Humans; Male; Female; Young Adult; Adult; Muscle Proteins; Whey Proteins; Collagen; Muscle, Skeletal; Eating; Polyesters; Postprandial Period; Dietary Proteins
PubMed: 37202878
DOI: 10.1249/MSS.0000000000003214 -
Marine Drugs Jul 2023Sarcopenia, a progressive disease characterized by a decline in muscle strength, quality, and mass, affects aging population worldwide, leading to increased morbidity... (Review)
Review
Sarcopenia, a progressive disease characterized by a decline in muscle strength, quality, and mass, affects aging population worldwide, leading to increased morbidity and mortality. Besides resistance exercise, various nutritional strategies, including omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation, have been sought to prevent this condition. This narrative review summarizes the current evidence on the effect and mechanism of n-3 PUFA on musculoskeletal health. Despite conflicting evidence, n-3 PUFA is suggested to benefit muscle mass and volume, with more evident effects with higher supplementation dose (>2 g/day). n-3 PUFA supplementation likely improves handgrip and quadriceps strength in the elderly. Improved muscle functions, measured by walking speed and time-up-to-go test, are also observed, especially with longer duration of supplementation (>6 months), although the changes are small and unlikely to be clinically meaningful. Lastly, n-3 PUFA supplementation may positively affect muscle protein synthesis response to anabolic stimuli, alleviating age-related anabolic resistance. Proposed mechanisms by which n-3 PUFA supplementation improves muscle health include 1. anti-inflammatory properties, 2. augmented expression of mechanistic target of rapamycin complex 1 (mTORC1) pathway, 3. decreased intracellular protein breakdown, 4. improved mitochondrial biogenesis and function, 5. enhanced amino acid transport, and 6. modulation of neuromuscular junction activity. In conclusion, n-3 PUFAs likely improve musculoskeletal health related to sarcopenia, with suggestive effect on muscle mass, strength, physical performance, and muscle protein synthesis. However, the interpretation of the findings is limited by the small number of participants, heterogeneity of supplementation regimens, and different measuring protocols.
Topics: Humans; Aged; Sarcopenia; Hand Strength; Muscle, Skeletal; Fatty Acids, Omega-3; Muscle Proteins; Dietary Supplements
PubMed: 37504930
DOI: 10.3390/md21070399 -
Nature Reviews. Molecular Cell Biology Sep 2023Actin plays many well-known roles in cells, and understanding any specific role is often confounded by the overlap of multiple actin-based structures in space and time.... (Review)
Review
Actin plays many well-known roles in cells, and understanding any specific role is often confounded by the overlap of multiple actin-based structures in space and time. Here, we review our rapidly expanding understanding of actin in mitochondrial biology, where actin plays multiple distinct roles, exemplifying the versatility of actin and its functions in cell biology. One well-studied role of actin in mitochondrial biology is its role in mitochondrial fission, where actin polymerization from the endoplasmic reticulum through the formin INF2 has been shown to stimulate two distinct steps. However, roles for actin during other types of mitochondrial fission, dependent on the Arp2/3 complex, have also been described. In addition, actin performs functions independent of mitochondrial fission. During mitochondrial dysfunction, two distinct phases of Arp2/3 complex-mediated actin polymerization can be triggered. First, within 5 min of dysfunction, rapid actin assembly around mitochondria serves to suppress mitochondrial shape changes and to stimulate glycolysis. At a later time point, at more than 1 h post-dysfunction, a second round of actin polymerization prepares mitochondria for mitophagy. Finally, actin can both stimulate and inhibit mitochondrial motility depending on the context. These motility effects can either be through the polymerization of actin itself or through myosin-based processes, with myosin 19 being an important mitochondrially attached myosin. Overall, distinct actin structures assemble in response to diverse stimuli to affect specific changes to mitochondria.
Topics: Actins; Mitochondria; Formins; Myosins; Endoplasmic Reticulum
PubMed: 37277471
DOI: 10.1038/s41580-023-00613-y -
Journal of the International Society of... Dec 2023Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of literature surrounding the effects of...
Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of literature surrounding the effects of essential amino acid (EAA) supplementation on skeletal muscle maintenance and performance. This position stand is intended to provide a scientific foundation to athletes, dietitians, trainers, and other practitioners as to the benefits of supplemental EAA in both healthy and resistant (aging/clinical) populations. EAAs are crucial components of protein intake in humans, as the body cannot synthesize them. The daily recommended intake (DRI) for protein was established to prevent deficiencies due to inadequate EAA consumption. The following conclusions represent the official position of the Society: 1. Initial studies on EAAs' effects on skeletal muscle highlight their primary role in stimulating muscle protein synthesis (MPS) and turnover. Protein turnover is critical for replacing degraded or damaged muscle proteins, laying the metabolic foundation for enhanced functional performance. Consequently, research has shifted to examine the effects of EAA supplementation - with and without the benefits of exercise - on skeletal muscle maintenance and performance. 2. Supplementation with free-form EAAs leads to a quick rise in peripheral EAA concentrations, which in turn stimulates MPS. 3. The safe upper limit of EAA intake (amount), without inborn metabolic disease, can easily accommodate additional supplementation. 4. At rest, stimulation of MPS occurs at relatively small dosages (1.5-3.0 g) and seems to plateau at around 15-18 g. 5. The MPS stimulation by EAAs does not require non-essential amino acids. 6. Free-form EAA ingestion stimulates MPS more than an equivalent amount of intact protein. 7. Repeated EAA-induced MPS stimulation throughout the day does not diminish the anabolic effect of meal intake. 8. Although direct comparisons of various formulas have yet to be investigated, aging requires a greater proportion of leucine to overcome the reduced muscle sensitivity known as "anabolic resistance." 9. Without exercise, EAA supplementation can enhance functional outcomes in anabolic-resistant populations. 10. EAA requirements rise in the face of caloric deficits. During caloric deficit, it's essential to meet whole-body EAA requirements to preserve anabolic sensitivity in skeletal muscle.
Topics: Humans; Leucine; Amino Acids; Muscle, Skeletal; Muscle Proteins; Dietary Supplements
PubMed: 37800468
DOI: 10.1080/15502783.2023.2263409 -
Sports Medicine (Auckland, N.Z.) Jul 2023Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates.
OBJECTIVE
We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise.
METHODS
Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous L-[ring-C]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates.
RESULTS
Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h, p = 0.440) protein synthesis rates.
CONCLUSIONS
Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ.
CLINICAL TRIAL REGISTRATION
NTR7251 .
Topics: Male; Humans; Caseins; Whey Proteins; Dietary Proteins; Sleep; Muscle Proteins; Mitochondrial Proteins; Eating; Muscle, Skeletal
PubMed: 36857005
DOI: 10.1007/s40279-023-01822-3 -
The Journal of Cell Biology Dec 2023Cellular actin networks exhibit a wide range of sizes, shapes, and architectures tailored to their biological roles. Once assembled, these filamentous networks are... (Review)
Review
Cellular actin networks exhibit a wide range of sizes, shapes, and architectures tailored to their biological roles. Once assembled, these filamentous networks are either maintained in a state of polarized turnover or induced to undergo net disassembly. Further, the rates at which the networks are turned over and/or dismantled can vary greatly, from seconds to minutes to hours or even days. Here, we review the molecular machinery and mechanisms employed in cells to drive the disassembly and turnover of actin networks. In particular, we highlight recent discoveries showing that specific combinations of conserved actin disassembly-promoting proteins (cofilin, GMF, twinfilin, Srv2/CAP, coronin, AIP1, capping protein, and profilin) work in concert to debranch, sever, cap, and depolymerize actin filaments, and to recharge actin monomers for new rounds of assembly.
Topics: Actin Cytoskeleton; Actin Depolymerizing Factors; Actins; Profilins; Mammals; Animals
PubMed: 37948068
DOI: 10.1083/jcb.202309021 -
Journal of Applied Physiology... Jan 2024Skeletal muscle is a highly complex tissue that is studied by scientists from a wide spectrum of disciplines, including motor control, biomechanics, exercise science,... (Review)
Review
Skeletal muscle is a highly complex tissue that is studied by scientists from a wide spectrum of disciplines, including motor control, biomechanics, exercise science, physiology, cell biology, genetics, regenerative medicine, orthopedics, and engineering. Although this diversity in perspectives has led to many important discoveries, historically, there has been limited overlap in discussions across fields. This has led to misconceptions and oversimplifications about muscle biology that can create confusion and potentially slow scientific progress across fields. The purpose of this synthesis paper is to bring together research perspectives across multiple muscle fields to identify common assumptions related to muscle fiber type that are points of concern to clarify. These assumptions include ) classification by myosin isoform and fiber oxidative capacity is equivalent, ) fiber cross-sectional area (CSA) is a surrogate marker for myosin isoform or oxidative capacity, and ) muscle force-generating capacity can be inferred from myosin isoform. We address these three fiber-type traps and provide some context for how these misunderstandings can and do impact experimental design, computational modeling, and interpretations of findings, from the perspective of a range of fields. We stress the dangers of generalizing findings about "muscle fiber types" among muscles or across species or sex, and we note the importance for precise use of common terminology across the muscle fields.
Topics: Biomechanical Phenomena; Muscle Fibers, Skeletal; Muscle, Skeletal; Myosins; Protein Isoforms; Biology; Myosin Heavy Chains
PubMed: 37994416
DOI: 10.1152/japplphysiol.00337.2023 -
European Heart Journal Jul 2023Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test...
AIMS
Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality.
METHODS AND RESULTS
Among adults without cardiovascular disease in the 1999-2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13-1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02-1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14-1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21-1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19-1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09-1.53) for Abbott after adjustment for the Ortho assay.
CONCLUSION
This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population.
Topics: Adult; Humans; Troponin I; Troponin T; Nutrition Surveys; Cardiovascular Diseases; Proportional Hazards Models; Biomarkers; Prognosis
PubMed: 37264651
DOI: 10.1093/eurheartj/ehad328 -
Annual Review of Biochemistry Jun 2023Muscles are essential for movement and heart function. Contraction and relaxation of muscles rely on the sliding of two types of filaments-the thin filament and the... (Review)
Review
Muscles are essential for movement and heart function. Contraction and relaxation of muscles rely on the sliding of two types of filaments-the thin filament and the thick myosin filament. The thin filament is composed mainly of filamentous actin (F-actin), tropomyosin, and troponin. Additionally, several other proteins are involved in the contraction mechanism, and their malfunction can lead to diverse muscle diseases, such as cardiomyopathies. We review recent high-resolution structural data that explain the mechanism of action of muscle proteins at an unprecedented level of molecular detail. We focus on the molecular structures of the components of the thin and thick filaments and highlight the mechanisms underlying force generation through actin-myosin interactions, as well as Ca-dependent regulation via the dihydropyridine receptor, the ryanodine receptor, and troponin. We particularly emphasize the impact of cryo-electron microscopy and cryo-electron tomography in leading muscle research into a new era.
Topics: Actins; Cryoelectron Microscopy; Muscle Contraction; Troponin; Myosins; Calcium
PubMed: 37001141
DOI: 10.1146/annurev-biochem-052521-042909