Chromium (Cr) compounds are markedly toxic and carcinogenic. Previously, we found that
Cr (VI) induced autophagy in A549 cells. Here, the effect of
mitochondrial dysfunction and endoplasmic reticulum (ER) stress on inducing mitophagy was investigated in both A549 and H1299 cells. Exposure to
Cr (VI) for 6 h significantly enhanced
reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (
MMP). Transmission electron microscopy showed that
Cr (VI) induced mitochondrial morphological changes, such as, mitochondrial swelling and vacuolization. The elevated expression of
GRP78 and p-PERK suggested that
Cr (VI) resulted in ER stress. Both
mitochondrial dysfunction and ER stress played an important role in
Cr (VI)-induced mitophagy, as the mitochondrial function inhibitor,
carbonyl cyanide 3-chlorophenylhydrazone (
CCCP) induced PINK1 and PARK2 and increased the expression of
GRP78 and p-PERK while the levels of
Cr (VI)-induced PINK1, PARK2, LC3-II were reduced after ER stress inhibitor, phenylbutyric
acid (4PBA) pretreatment. When A549 cells were treated with
CCCP and
4-PBA simultaneously,
CCCP-induced expressions of PINK1, PARK2 and LC3-II decreased significantly compared with that of only
CCCP-treated cells, indicating that there was a crosstalk between mitochondria and ER in inducing mitophagy. Additionally, the crosstalk between
mitochondrial dysfunction and ER stress modulated the expression of
Cr (VI)-induced ATF4, which resulted in mitophagy. Collectively, our data demonstrated that
Cr (VI)-induced mitophagy mediated by ATF4 via the crosstalk between ER stress and
mitochondrial dysfunction.