INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
Adaptive downregulation of mitochondrial function in down syndrome.
Autor/es:
HELGUERA P.; SEIGLIE J.; RODRIGUEZ J. A.; HANNA M.; HELGUERA G.; BUSCIGLIO J.
Revista:
CELL METABOLISM
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2013 p. 132 - 140
ISSN:
1550-4131
Resumen:
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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.