Preliminary observations of mitochondrial dysfunction in Prader–Willi syndrome
Year: 2018
Type: article
Abstract: Prader-Willi syndrome (PWS) is a complex multisystem disorder because of errors in genomic imprinting with severe hypotonia, decreased muscle mass, poor suckling, feeding problems and failure to thrive during infancy, growth and other hormone deficiency, childhood-onset hyperphagia, and subsequent obesity. Decreased energy expenditure in PWS is thought to contribute to reduced muscle mass and physical activity but may also relate to cellular metabolism and disturbances in mitochondrial function. We established fibroblast cell lines from six children and adults with PWS and six healthy controls for mitochondrial assays. We used Agilent Seahorse XF extracellular flux technology to determine real-time measurements of several metabolic parameters including cellular substrate utilization, Adenosine Triphosphate (ATP)-linked respiration, and mitochondrial capacity in living cells. Decreased mitochondrial function was observed in the PWS patients compared to the healthy controls with significant differences in basal respiration, maximal respiratory capacity, and ATP-linked respiration. These results suggest disturbed mitochondrial bioenergetics in PWS although the low number of studied subjects will require a larger subject population before a general consensus can be reached to identify if mitochondrial dysfunction is a contributing factor in PWS.
DOI: 10.1002/ajmg.a.40526
Institution: University of Kansas Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1223950664, G1263914652, G1377672508, Organelle Specific Oxidative Stress Response in Environmental Toxin-Induced Cellular Dysfunction, G3900448260, G466018729, Mechanisms of Liver Injury and Diseases, G5895133988, G602775177, Kansas Intellectual and Developmental Disabilities Research Center (KIDDRC), Center for Cancer Biology
OpenAlex ID: W2894645585