Research Paper Volume 7, Issue 9 pp 629—643

PGC-1α controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity


Figure 6. Schematic representation of adaptive response and neuroprotection induced by cell-tolerated levels of Pb2+. Exposure to non-cytotoxic levels of lead (100μM) induces an adaptive biological response. This response involves ER calcium release and requires both caspase-8 activation and BAP31 cleavage (1). Increased cytoplasmic levels of calcium induce expression and activation of calcineurin (2) as well as an increase in PGC1α expression. Subsequently, PGC1α stimulates its own expression and the expression of mitochondrial biogenesis (NRF1, NRF2, TMFA) and dynamics (DRP1and MFN1) genes (3). A shift of mitochondrial dynamics towards fusion renders neuronal cells more resistant to lead insult (4-5).