Abstract:
:Mitochondrial dysfunction plays an important role in the etiology of neurodegenerative diseases. However, the progressive nature of neuronal loss in genetic models of mitochondrial dysfunction suggests the presence of compensatory mechanisms promoting neuronal survival under these conditions. Here, we identified the energy metabolism kinase LKB1 as a key regulator of the compensatory mechanisms activated in neurons, following mitochondrial dysfunction. To accomplish this, we have created an in vivo neurodegenerative model based on the deletion of the mitochondrial protein apoptosis-inducing factor (AIF) in postmitotic neurons. Loss of mitochondrial function caused by AIF deletion induced several adaptive mechanisms, including increased glycolysis and mitochondrial biogenesis. Importantly, the activation of these adaptive mechanisms was abrogated by the deletion of one allele of LKB1, resulting in impaired neuronal survival. Because loss of mitochondrial function is a central mechanism implicated in neurodegenerative diseases, modulation of LKB1-dependent pathways may represent an important strategy to preserve neuronal survival and function.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Germain M,Nguyen AP,Khacho M,Patten DA,Screaton RA,Park DS,Slack RSdoi
10.1093/hmg/dds500subject
Has Abstractpub_date
2013-03-01 00:00:00pages
952-62issue
5eissn
0964-6906issn
1460-2083pii
dds500journal_volume
22pub_type
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