Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis

BECKERVORDERSANDFORTH R; EBERT B; SCHAFFNER I; MOSS J; FIEBIG C; SHIN J; MOORE D; GHOSH L; TRINCHERO MF; STOCKBURGER C; FRIEDLAND K; STEIB K; VON WITTGENSTEIN J; KEINER S; REDECKER C; HOLTER S; XIANG W; WURST W; JAGASIA R; SCHINDER AF; MING G; TONI N; JESSBERGER S; SONG H; LIE C

NEURON

CELL PRESS

Lugar: United States; Año: 2017 vol. 93 p. 560 - 573

0896-6273

Precise regulation of cellular metabolism is hypothesizedto constitute a vital component of the developmentalsequence underlying the life-long generationof hippocampal neurons from quiescentneural stem cells (NSCs). The identity of stage-specificmetabolic programs and their impact on adultneurogenesis are largely unknown. We show thatthe adult hippocampal neurogenic lineage is criticallydependent on the mitochondrial electrontransport chain and oxidative phosphorylationmachinery at the stage of the fast proliferating intermediateprogenitor cell. Perturbation of mitochondrialcomplex function by ablation of the mitochondrialtranscription factor A (Tfam) reproducesmultiple hallmarks of aging in hippocampal neurogenesis,whereas pharmacological enhancementof mitochondrial function ameliorates age-associatedneurogenesis defects. Together with thefinding of age-associated alterations in mitochondrialfunction and morphology in NSCs, thesedata link mitochondrial complex function to efficientlineage progression of adult NSCs and identifymitochondrial function as a potential targetto ameliorate neurogenesis-defects in the aginghippocampus.