RESUMEN
The common-bean (Phaseolus vulgaris), a widely consumed legume, originated in Mesoamerica and expanded to South America, resulting in the development of two geographically distinct gene pools. Poor soil condition, including metal toxicity, are often constraints to common-bean crop production. Several P. vulgaris miRNAs, including miR1511, respond to metal toxicity. The MIR1511 gene sequence from the two P. vulgaris model sequenced genotypes revealed that, as opposed to BAT93 (Mesoamerican), the G19833 (Andean) accession displays a 58-bp deletion, comprising the mature and star miR1511 sequences. Genotyping-By-Sequencing data analysis from 87 non-admixed Phaseolus genotypes, comprising different Phaseolus species and P. vulgaris populations, revealed that all the P. vulgaris Andean genotypes and part of the Mesoamerican (MW1) genotypes analyzed displayed a truncated MIR1511 gene. The geographic origin of genotypes with a complete versus truncated MIR1511 showed a distinct distribution. The P. vulgaris ALS3 (Aluminum Sensitive Protein 3) gene, known to be important for aluminum detoxification in several plants, was experimentally validated as the miR1511 target. Roots from BAT93 plants showed decreased miR1511 and increased ALS3 transcript levels at early stages under aluminum toxicity (AlT), while G19833 plants, lacking mature miR1511, showed higher and earlier ALS3 response. Root architecture analyses evidenced higher tolerance of G19833 plants to AlT. However, G19833 plants engineered for miR1511 overexpression showed lower ALS3 transcript level and increased sensitivity to AlT. Absence of miR1511 in Andean genotypes, resulting in a diminished ALS3 transcript degradation, appears to be an evolutionary advantage to high Al levels in soils with increased drought conditions.
Asunto(s)
Aluminio/toxicidad , MicroARNs/genética , Phaseolus/genética , ARN de Planta/genética , Eliminación de Gen , Variación Genética , MicroARNs/metabolismo , Phaseolus/efectos de los fármacos , Phaseolus/metabolismo , Raíces de Plantas/crecimiento & desarrollo , ARN de Planta/metabolismo , Estrés FisiológicoRESUMEN
BACKGROUND: Restoring normal mitochondrial function represents a new target for strategies aimed at mitigating the stress response to severe burn trauma and hastening recovery. Our objective was to investigate the determinants of skeletal muscle mitochondrial respiratory capacity and function and its association with glucose metabolism and functional capacity in burned children. METHODS: Data from burned children enrolled in the placebo arm of an ongoing prospective clinical trial were analyzed. Mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry on at least one occasion per participant. In subsets of patients, glucose kinetics and cardiorespiratory fitness (VO2peak) were also determined. Mixed multiple regression models were used to identify the determinants of mitochondrial respiratory function and to assess the relationship between mitochondrial respiration and both glucose control and functional capacity (VO2peak). MAIN RESULTS: Increasing full-thickness burn size was associated with greater adjusted coupled (ATP-producing) respiration, adjusted for age, sex, sepsis, and time of testing (Pâ<â0.01; nâ=â55, obsâ=â97). Girls had on average 23.3% lower coupled respiration (adjusted mean and 95% confidence of interval [CI], -7.1; -12.6 to -1.7 pmol/s/mg; Pâ<â0.025) and 29.8% lower respiratory control than boys (adjusted mean and 95% CI, -0.66; -1.07 to -0.25; Pâ<â0.01; nâ=â55, obsâ=â97). The presence of sepsis was associated with lower respiration coupled to ATP production by an average of 25.5% compared with nonsepsis (adjusted mean and 95% CI, -6.9; -13.0 to -0.7 pmol/s/mg; Pâ<â0.05; nâ=â55, obsâ=â97), after adjustment for age, sex, full-thickness burn size, and time of testing. During a hyperinsulinemic euglycemic clamp, hepatic glucose release was associated with greater coupled respiration and respiratory control (Pâ<â0.05; nâ=â42, obsâ=â73), independent of age, sepsis, full-thickness burn size, and time postinjury testing. Coupled respiration was positively associated with VO2peak after adjustment for age, full-thickness burn size, and time of exercise testing (Pâ<â0.025; nâ=â18, obsâ=â25). CONCLUSIONS: Burn severity, sex, and sepsis influence skeletal muscle mitochondrial function in burned children. Glucose control and functional capacity are associated with altered mitochondrial respiratory function in muscle of burn survivors, highlighting the relationship of altered muscle bioenergetics with the clinical sequelae accompanying severe burn trauma.