Adaptive downregulation of mitochondrial function in down syndrome.

HELGUERA P.; SEIGLIE J.; RODRIGUEZ J. A.; HANNA M.; HELGUERA G.; BUSCIGLIO J.

CELL METABOLISM

CELL PRESS

Lugar: United States; Año: 2013 p. 132 - 140

1550-4131

 <!-- /* Font Definitions */ @font-face {font-family:"Times New Roman"; panose-1:0 2 2 6 3 5 4 5 2 3; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:50331648 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman";} table.MsoNormalTable {mso-style-parent:""; font-size:10.0pt; font-family:"Times New Roman";} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> Mitochondrial dysfunction and oxidative stress are common features of Down syndrome (DS). However, the underlying mechanisms are not known. We investigated the relationship between abnormal energy metabolism and oxidative stress with tran- scriptional and functional changes in DS cells. Impaired mitochondrial activity correlated with altered mitochondrial morphology. Increasing fusion capacity prevented morphological but not functional alterations in DS mitochondria. Sustained stimula- tion restored mitochondrial functional parameters but increased reactive oxygen species production and cell damage, suggesting that reduced DS mito- chondrial activity is an adaptive response for avoid- ing injury and preserving basic cellular functions. Network analysis of genes overexpressed in DS cells demonstrated functional integration in path- ways involved in energy metabolism and oxidative stress. Thus, although preventing extensive oxida- tive damage, mitochondrial downregulation may contribute to increased susceptibility of individuals with DS to clinical conditions in which altered energy metabolism may play a role, such as Alzheimer?s disease, diabetes, and some types of autistic spec- trum disorders.