page 1151, protective responses are also sent along. Their results are the first demonstration of a signaling pathway from the ER to mitochondria to initiate adaptive changes that support cellular respiration when protein synthesis is disturbed.
Certain cellular stresses, such as low oxygen or disturbance of Ca2+ levels, cause the accumulation of unfolded proteins in the ER. To limit the load on the ER, cytoplasmic protein synthesis is reduced and protein degradation rates increase. However, transcription and translation of several stress responsive genes increase. Hori's group has identified a mitochondrial ATP-dependent protease, Lon, as one such stress-induced gene.
Lon supports mitochondrial function by facilitating assembly of essential mitochondrial proteins. ER stress caused a reduction in levels of cytochrome c oxidase (COX) subunits and the accumulation of unfolded COX proteins at the mitochondria. Overexpression of Lon in cell culture increased the amount of correctly folded COX subunits. As a result, mitochondria were less likely to lose their membrane potential during stress conditions. Hori expects that mice lacking this chaperone activity will be more sensitive to conditions that cause ER stress and plans to test this theory in Lon knock-out mice. ▪