Wearable robots are often powered by elastic actuators, which can mimic the intrinsic compliance observed in human joints, contributing to safe and seamless interaction. However, due to their increased complexity, when compared to direct drives, elastic actuators are susceptible to faults, which pose significant challenges, potentially compromising user experience and safety during interaction. In this article, we developed a fault-tolerant control strategy for torque assistance in a knee exoskeleton and investigated user experience during a walking task while emulating faults.
View Article and Find Full Text PDFMfn2 is a mitochondrial outer membrane fusion protein with the additional role of tethering mitochondria to the ER. Here, we describe a novel connection between Mfn2 and calcium release from mitochondria. We show that Mfn2 controls the mitochondrial inner membrane sodium-calcium exchange protein NCLX, which is a major source for calcium release from mitochondria.
View Article and Find Full Text PDFThe dynamin-related guanosine triphosphatase, Drp1 (encoded by ), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice.
View Article and Find Full Text PDFUsing the seminal rubber hand illusion and related paradigms, the last two decades unveiled the multisensory mechanisms underlying the sense of limb embodiment, that is, the cognitive integration of an artificial limb into one's body representation. Since also individuals with amputations can be induced to embody an artificial limb by multimodal sensory stimulation, it can be assumed that the involved computational mechanisms are universal and independent of the perceiver's physical integrity. This is anything but trivial, since experimentally induced embodiment has been related to the embodiment of prostheses in limb amputees, representing a crucial rehabilitative goal with clinical implications.
View Article and Find Full Text PDFRecent breakthroughs in live-cell imaging have enabled visualization of cristae, making it feasible to investigate the structure-function relationship of cristae in real time. However, quantifying live-cell images of cristae in an unbiased way remains challenging. Here, we present a novel, semi-automated approach to quantify cristae, using the machine-learning Trainable Weka Segmentation tool.
View Article and Find Full Text PDFThe mitochondrial membrane potential (ΔΨ ) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), is considered to carry a uniform ΔΨ . However, sequestration of OXPHOS components in cristae membranes necessitates a re-examination of the equipotential representation of the IMM.
View Article and Find Full Text PDFMitochondrial shaping proteins are categorized as fusion and fission factors based on their opposing actions on the architecture of mitochondria. Mammalian Fis1 fragments mitochondria into small units and was initially considered a major mitochondrial fission factor, with this major role being challenged. Yu (2019) define that Fis1 induces mitochondrial fragmentation by blocking mitochondrial fusion.
View Article and Find Full Text PDFObjective: Mitochondria are organelles primarily responsible for energy production, and recent evidence indicates that alterations in size, shape, location, and quantity occur in response to fluctuations in energy supply and demand. We tested the impact of acute and chronic exercise on mitochondrial dynamics signaling and determined the impact of the mitochondrial fission regulator Dynamin related protein (Drp)1 on exercise performance and muscle adaptations to training.
Methods: Wildtype and muscle-specific Drp1 heterozygote (mDrp1) mice, as well as dysglycemic (DG) and healthy normoglycemic men (control) performed acute and chronic exercise.
Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin.
View Article and Find Full Text PDFEstrogen receptor α (ERα) action plays an important role in pancreatic β-cell function and survival; thus, it is considered a potential therapeutic target for the treatment of type 2 diabetes in women. However, the mechanisms underlying the protective effects of ERα remain unclear. Because ERα regulates mitochondrial metabolism in other cell types, we hypothesized that ERα may act to preserve insulin secretion and promote β-cell survival by regulating mitochondrial-endoplasmic reticulum (EndoRetic) function.
View Article and Find Full Text PDFMitochondria are best known for harboring pathways involved in ATP synthesis through the tricarboxylic acid cycle and oxidative phosphorylation. Major advances in understanding these roles were made with mutants affecting key components of the metabolic pathways. These mutants have not only helped elucidate some of the intricacies of metabolism pathways, but they have also served as jumping off points for pharmacology, toxicology, and aging studies.
View Article and Find Full Text PDFA fascinating story is unfolding at the interface between mitochondria and the ER. Two new papers, one in this issue of EMBO (Wu , 2016) and one in the journal (Chen , 2016), further clarify the role of mitochondrial outer membrane protein FUNDC1 in autophagy and connect it to mitochondrial fission occurring at the interface between mitochondria and the ER.
View Article and Find Full Text PDFAutocrine VEGF is necessary for endothelial survival, although the cellular mechanisms supporting this function are unknown. Here, we show that--even after full differentiation and maturation--continuous expression of VEGF by endothelial cells is needed to sustain vascular integrity and cellular viability. Depletion of VEGF from the endothelium results in mitochondria fragmentation and suppression of glucose metabolism, leading to increased autophagy that contributes to cell death.
View Article and Find Full Text PDFDynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)-driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin.
View Article and Find Full Text PDFThe mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex "mitochondrial contact site and cristae organizing system" and its subunits Mic10 to Mic60.
View Article and Find Full Text PDFDamaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson's disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation.
View Article and Find Full Text PDFTrichomonas vaginalis is a highly divergent, unicellular eukaryote of the phylum Metamonada, class Parabasalia, and the source of a common sexually transmitted infection. This parasite lacks mitochondria, but harbors an evolutionarily related organelle, the hydrogenosome. We explored the role of dynamin-related proteins (DRPs) in the division of the hydrogenosome.
View Article and Find Full Text PDFMitochondrial fission is mediated by the dynamin-related protein Drp1 in metazoans. Drp1 is recruited from the cytosol to mitochondria by the mitochondrial outer membrane protein Mff. A second mitochondrial outer membrane protein, named Fis1, was previously proposed as recruitment factor, but Fis1(-/-) cells have mild or no mitochondrial fission defects.
View Article and Find Full Text PDFMitochondria continually change shape through the combined actions of fission, fusion, and movement along cytoskeletal tracks. The lengths of mitochondria and the degree to which they form closed networks are determined by the balance between fission and fusion rates. These rates are influenced by metabolic and pathogenic conditions inside mitochondria and by their cellular environment.
View Article and Find Full Text PDFMitochondrial cristae morphology is highly variable and altered under numerous pathological conditions. The protein complexes involved are largely unknown or only insufficiently characterized. Using complexome profiling we identified apolipoprotein O (APOO) and apolipoprotein O-like protein (APOOL) as putative components of the Mitofilin/MINOS protein complex which was recently implicated in determining cristae morphology.
View Article and Find Full Text PDFMitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress.
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