Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans

Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)–based proteolysis and, consequentially, muscle cell dystrophy. We found that inhibition of the mitochondrial electron transport chain causes paralysis as well as muscle structural damage in the nematode Caenorhabditis elegans. This was associated with a significant decline in collagen content. Both paralysis and muscle damage could be rescued with collagen IV overexpression, matrix metalloproteinase (MMP), and Furin inhibitors in Antimycin A–treated animal as well as in the C. elegans Duchenne muscular dystrophy model. Additionally, muscle cytosolic calcium increased in the Antimycin A–treated worms, and its down-regulation rescued the muscle damage, suggesting that calcium overload acts as one of the early triggers and activates Furin and MMPs for collagen degradation. In conclusion, we have established ECM degradation as an important pathway of muscle damage

Comparative Analysis of Muscle Atrophy During Spaceflight, Nutritional Deficiency and Disuse in the Nematode Caenorhabditis elegans

While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy

A stratagem for primary root elongation under moderate salt stress in the halophyte Schrenkiella parvula [2]

Schrenkiella parvula, an Arabidopsis-related halophyte, grows around Lake Tuz (Salt) in Turkey and can survive up to 600 mM NaCl. Here, we performed physiological studies on the roots of S. parvula and A. thaliana seedlings cultivated under a moderate salt condition (100 mM NaCl). Interestingly, S. parvula germinated and grew at 100 mM NaCl, but germination did not occur at salt concentrations above 200 mM. In addition, primary roots elongated much faster at 100 mM NaCl, while being thinner with fewer roots hair, than under NaCl-free conditions. Salt-induced root elongation was due to epidermal cell elongation, but meristem size and meristematic DNA replication were reduced. The expression of genes related to auxin response and biosynthesis was also reduced. Application of exogenous auxin abolished the changes in primary root elongation, suggesting that auxin reduction is the main trigger for root architectural changes in response to moderate salinity in S. parvula. In A. thaliana seeds, germination was maintained up to 200 mM NaCl, but post-germination root elongation was significantly inhibited. Furthermore, primary roots did not promote elongation even under fairly low salt conditions. Compared to A. thaliana, cell death and ROS content in primary roots of salt-stressed plants were significantly lower in S. parvula. These changes in the roots of S. parvula seedlings may be an adaptive strategy to reach lower salinity by advancing into deeper soils, while being impaired by moderate salt stress.Japan Society for the Promotion of Science,Grant/Award Number: JP18H0394This work was supported in part by JSPS KAKENHI grant number JP18H03947 (Atsushi Higashitani). Keriman Sekerci obtained a scholarship from the Ministry of Education, Culture, Sports, Science, andTechnology (MEXT)Japan Society for the Promotion of Science [JP18H0394]; JSPS KAKENHI [JP18H03947]; Ministry of Education, Culture, Sports, Science, and Technology (MEXT

Loss of physical contact in space alters the dopamine system in <i>C.</i> <i>elegans</i>

Progressive neuromuscular decline in microgravity is a prominent health concern preventing interplanetary human habitation. We establish functional dopamine-mediated impairments as a consistent feature across multiple spaceflight exposures and during simulated microgravity in C. elegans. Animals grown continuously in these conditions display reduced movement and body length. Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and comt-4 (catechol-O-methyl transferase) expression levels. The application of exogenous dopamine reverses the movement and body length defects caused by simulated microgravity. In addition, increased physical contact made comt-4 and dopamine levels rise. It also increased muscular cytoplasmic Ca2+ firing. In dop-3 (D2-like receptor) mutants, neither decrease in movement nor in body length were observed during simulated microgravity growth. These results strongly suggest that targeting the dopamine system through manipulation of the external environment (contact stimuli) prevents muscular changes and is a realistic and viable treatment strategy to promote safe human deep-space travel