FGF21 as Modulator of Metabolism in Health and Disease

Fibroblast growth factor 21 (FGF21) is a hormone that regulates important metabolic pathways. FGF21 is expressed in several metabolically active organs and interacts with different tissues. The FGF21 function is complicated and well debated due to its different sites of production and actions. Striated muscles are plastic tissues that undergo adaptive changes within their structural and functional properties in order to meet their different stresses, recently, they have been found to be an important source of FGF21. The FGF21 expression and secretion from skeletal muscles happen in both mouse and in humans during their different physiological and pathological conditions, including exercise and mitochondrial dysfunction. In this review, we will discuss the recent findings that identify FG21 as beneficial and/or detrimental cytokine interacting as an autocrine or endocrine in order to modulate cellular function, metabolism, and senescence

Percolating Superconductivity in Air-Stable Organic-Ion Intercalated MoS2

When doped into a certain range of charge carrier concentrations, MoS2 departs from its pristine semiconducting character to become a strongly correlated material characterized by exotic phenomena such as charge density waves or superconductivity. However, the required doping levels are typically achieved using ionic-liquid gating or air-sensitive alkali-ion intercalation, which are not compatible with standard device fabrication processes. Here, we report on the emergence of superconductivity and a charge density wave phase in air-stable organic cation intercalated MoS2 crystals. By selecting two different molecular guests, we show that these correlated electronic phases depend dramatically on the intercalated cation, demonstrating the potential of organic ion intercalation to finely tune the properties of 2D materials. Moreover, we find that a fully developed zero-resistance state is not reached in few-nm-thick flakes, indicating the presence of three-dimensional superconductive paths which are severed by the mechanical exfoliation. We ascribe this behavior to an inhomogeneous charge carrier distribution, which we probe at the nanoscale using scanning near-field optical microscopy. Our results establish organic-ion intercalated MoS2 as a platform to study the emergence and modulation of correlated electronic phases

Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence

Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging

Transcription Factor EB Controls Metabolic Flexibility during Exercise

The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism

Biology of Lysiphlebus fabarum following cold storage of larvae and pupae

Citation: Mahi, H., Rasekh, A., Michaud, J. P., & Shishehbor, P. (2014). The biology of Lysiphlebus fabarum (Braconidae, Aphidiinae) following cold storage of larvae and pupae. Retrieved from http://krex.ksu.eduCold storage is a one means of preserving parasitoids prior to release in augmentation biological control programs. This study examined the feasibility of storing larval and pupal stages of a sexual population of Lysiphlebus fabarum Marshall (Braconidae: Aphidiinae) at 6.0 and 8.0 °C (± 1.0 °C), 50–60% RH, and 14L:10D photoperiod. These life stages were stored for periods of 1, 2 and 3 weeks under fluctuating thermal regimes (2.0 h daily at 21.0 ± 1.0 °C). Generally, pupae gave better results than larvae, 6.0 °C was better than 8.0 °C, and were better than constant, considering wasp survival, wasp size (tibial and antennal lengths), egg load and egg size. The best results were obtained with pupae stored for two weeks under a fluctuating temperature regime at 6.0 °C. Females emerging from this treatment did not differ from controls (developing directly at 21.0 °C) in body size, egg size, or progeny sex ratio and suffered less than 20% mortality. Egg loads were reduced in these wasps, but the reductions were substantially less than occurred in other two week storage treatments. Wasps stored in this manner successfully parasitized similar numbers of aphids as controls and produced similar progeny sex ratios. These results reveal a suitable set of low temperature conditions that can be used to delay the development of L. fabarum for two weeks with minimal impacts on wasp fitness

defective mitochondrial trna taurine modification activates global proteostress and leads to mitochondrial disease

Summary: A subset of mitochondrial tRNAs (mt-tRNAs) contains taurine-derived modifications at 34U of the anticodon. Loss of taurine modification has been linked to the development of mitochondrial diseases, but the molecular mechanism is still unclear. Here, we showed that taurine modification is catalyzed by mitochondrial optimization 1 (Mto1) in mammals. Mto1 deficiency severely impaired mitochondrial translation and respiratory activity. Moreover, Mto1-deficient cells exhibited abnormal mitochondrial morphology owing to aberrant trafficking of nuclear DNA-encoded mitochondrial proteins, including Opa1. The mistargeted proteins were aggregated and misfolded in the cytoplasm, which induced cytotoxic unfolded protein response. Importantly, application of chemical chaperones successfully suppressed cytotoxicity by reducing protein misfolding and increasing functional mitochondrial proteins in Mto1-deficient cells and mice. Thus, our results demonstrate the essential role of taurine modification in mitochondrial translation and reveal an intrinsic protein homeostasis network between the mitochondria and cytosol, which has therapeutic potential for mitochondrial diseases. : Taurine modification of mitochondrial tRNA is associated with mitochondrial disease. Fakruddin et al. find that taurine modification is indispensable for mitochondrial protein translation. The authors also find that deficiency of taurine modification impairs a mitochondrial-cytosolic proteostatic network through an Opa1-dependent mechanism and demonstrate the therapeutic potential of chemical chaperones. Keywords: tRNA, modification, taurine, mitochondria, Opa

Tuning the magnetic properties of NiPS3through organic-ion intercalation

Atomically thin van der Waals magnetic crystals are characterized by tunable magnetic properties related to their low dimensionality. While electrostatic gating has been used to tailor their magnetic response, chemical approaches like intercalation remain largely unexplored. Here, we demonstrate the manipulation of the magnetism in the van der Waals antiferromagnet NiPS3 through the intercalation of different organic cations, inserted using an engineered two-step process. First, the electrochemical intercalation of tetrabutylammonium cations (TBA+) results in a ferrimagnetic hybrid compound displaying a transition temperature of 78 K, and characterized by a hysteretic behavior with finite remanence and coercivity. Then, TBA+ cations are replaced by cobaltocenium via an ion-exchange process, yielding a ferrimagnetic phase with higher transition temperature (98 K) and higher remanent magnetization. Importantly, we demonstrate that the intercalation and cation exchange processes can be carried out in bulk crystals and few-layer flakes, opening the way to the integration of intercalated magnetic materials in devices.The authors acknowledge R. Llopis and A. Eleta for technical support. This work is supported by “la Caixa” Foundation (ID 100010434), under the agreement LCF/BQ/PI19/11690017, by the Spanish MICINN under Project PID2019-108153GA-I00, RTI2018-094861-B-100 and under the María de Maeztu Units of Excellence Program (MDM-2016-0618). B. M.-G. thanks Gipuzkoa Council (Spain) in the frame of Gipuzkoa Fellows Program.Peer reviewe