3 Papers found (0.011 seconds)

Vogel A et al. (2024) Nat Commun "UNC-45 assisted myosin folding depends on a conserved FX₃HY motif implicated in Freeman Sheldon Syndrome."

Meinhart A, Gudino Carrillo RM, Sehr D, Bylicki A, Arnese R, Vogel A, Deszcz L, Clausen T

[

Nat Commun,

2024]

Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX3HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX3HY motif linked to the Freeman Sheldon Syndrome impairs UNC-45 assisted folding, reducing the level of functional myosin. These findings demonstrate that a faulty myosin quality control is a critical yet unexplored cause of human myopathies.

Liao JF et al. (2025) Curr Res Food Sci "A comprehensive approach, based on the use of Caenorhabditis elegans, mouse, and human models, elucidates the impact of Lactiplantibacillus plantarum TWK10 on exercise performance and longevity."

Lin JS, Young SL, Hsu HY, Lee CC, Wang MF, Lee MC, Huang CC, Liao JF, Watanabe K

[

Curr Res Food Sci,

2025]

The functionality of probiotics is highly influenced by culture and processing conditions, making batch stability validation through human or mouse trials impractical. Here, we employed a comprehensive approach using Caenorhabditis elegans, mouse and human models to elucidate the beneficial effects of Lactiplantibacillus plantarum TWK10 (TWK10). In C. elegans, TWK10 administration significantly prolonged lifespan by 26.1 ± 11.9 % (p < 0.05), enhanced locomotion (p < 0.01) and muscle mass (p < 0.001), elevated glycogen storage (p < 0.05), and reduced lipid accumulation (p < 0.001), outperforming Lacticaseibacillus rhamnosus GG and L. plantarum type strain ATCC 14917T. We also confirmed the equivalence of laboratory-prepared and mass-produced TWK10 in ergogenic efficacy using C. elegans assay. In mice, oral administration of mass-produced TWK10 significantly enhanced exercise performance and glycogen storage in muscle and liver in a dose-dependent manner. In a clinical study involving healthy male adults, significant improvements in grip strength (1.1-fold, p < 0.01) and exhaustion time (1.27-fold, p < 0.01), and significant reductions in circulating lactate and ammonia levels were observed in the TWK10 group (1 × 1010 colony-forming unit/day) compared to the control group. Both humans and mice receiving mass-produced TWK10 showed improved body composition with increased muscle mass and reduced fat mass. In conclusion, TWK10 demonstrates superior longevous and ergogenic effects in C. elegans compared to reference strains. The consistent ergogenic efficacy of mass-produced TWK10 across C. elegans, mice, and humans, highlights the utility of C. elegans as a reliable model for probiotic research and industrial application.

Belogrudov GI et al. (2001) Arch Biochem Biophys "Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis."

Jonassen T, Gin P, Belogrudov GI, Clarke CF, Lee PT, Hsu AY

[

Arch Biochem Biophys,

2001]

The COQ4 gene coding for a component of the coenzyme Q biosynthetic pathway in the yeast Saccharomyces cerevisiae was cloned by a functional complementation of a Q-deficient mutant strain. Yeast coq4 mutant strains harboring the COQ4 gene on either single- or multicopy plasmids acquired the ability to grow on media containing a nonfermentable carbon source, synthesize Q(6), and respire. COQ4 encodes a polypeptide containing 335 amino acids with a calculated molecular mass of 38.6 kDa. By Western blot analysis with a specific antiserum, Coq4p was shown to peripherally associate with the matrix face of the mitochondrial inner membrane. The putative mitochondrial-targeting sequence present at the amino-terminus of the polypeptide efficiently imported it to mitochondria in a membrane-potential-dependent manner. Steady-state levels of COQ4 mRNA were increased during growth on glycerol-containing medium, in accordance with a function in Q biosynthesis. The function of Coq4p is unknown, although its presence is required to maintain a steady-state level of Coq7p, another component of the Q biosynthetic pathway. The results presented here, along with those available from literature, are discussed in light of the recently proposed existence of a multisubunit complex functioning in Q biosynthesis (A. Y. Hsu, T. Q. Do, P. T. Lee, and C. F. Clarke, 2000, Biochim. Biophys. Acta 1484, 287-297).