Alive via autophagy

By examining mouse embryonic fibroblasts, molecular biologist Gregg Semenza of The Johns Hopkins University School of Medicine and colleagues found that cells use autophagy to survive low oxygen conditions.

Jef Akst
Jef Akst
Feb 28, 2010

Alive via autophagy

Huafeng Zhang and Gregg Semenza, The Johns Hopkins University School of Medicine

The paper:
H. Zhang, et al., “Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia,” J Biol Chem, 283:10892–903, 2008. (Cited in 72 papers)

The finding:
By examining mouse embryonic fibroblasts, molecular biologist Gregg Semenza of The Johns Hopkins University School of Medicine and colleagues found that cells use autophagy to survive low oxygen conditions. Specifically, they showed that cells digest their mitochondria—a process known as mitochondrial autophagy—when deprived of oxygen, thereby halting oxidative metabolism, which would normally produce extra reactive oxygen species (ROS) during hypoxia. “The [cessation of oxidative metabolism] occurs not because there’s not enough oxygen to generate ATP, but to do so under hypoxic conditions would generate so much ROS, you’d kill the cell,” Semenza says.

The surprise:
“For the last 5 years or more, autophagy has been seen as a...

The mechanism:
Comparing wild-type cells to cells lacking the α-subunit of hypoxia-inducible factor 1 (HIF-1α), Semenza’s group further showed that mitochondrial autophagy is dependent on HIF-1—a key player in oxygen homeostasis—which “orchestrates a shift from oxidative to glycolytic metabolism,” Semenza says.

The implication:
A study by Pouysségur and others added more details to the process and showed that it occurs in tumor cells as well, suggesting that it may be a survival mechanism that promotes tumor growth.

Percent decrease in oxidative metabolism (as measured by amount of mitochondrial DNA) in cells under hypoxic conditions:
Wild-type: 75%
HIF-1α knockout: 0.067%