Findings shed light on Alzheimer's, Parkinson's, cancer
Scientists at The Scripps Research Institute (TSRI) have discovered a natural mechanism that cells use to protect mitochondria, the tiny but essential "power plants" that provide chemical energy for cells throughout the body. Damage to mitochondria is thought to be a significant factor in common neurodegenerative disorders, cancer and even the aging process. The TSRI researchers' discovery could lead to new methods for protecting mitochondria from such damage, thereby improving human health.
"The mechanism that we've identified potentially gives us another way to treat the many disorders that involve mitochondrial dysfunction," said R. Luke Wiseman, the Arlene and Arnold Goldstein Assistant Professor in TSRI's Department of Molecular & Experimental Medicine.
Wiseman was the senior author of the new study, which appears in the December 3, 2013 issue of the journal Cell Metabolism.
Power Plants of the Cell
Mitochondria are microscopic reactors that burn oxygen to make ATP, the basic unit of chemical energy in cells. As such, they are the major consumers of the oxygen we breathe.
But the oxygen molecules concentrated within mitochondria are highly reactive, tending to modify proteins in unwanted ways, changing them into abnormal shapes and often causing them to become dysfunctional and clump together. If this misfolding and aggregation gets out of control-induced by factors including genetic mutations, aging and environmental toxins such as pesticides-the result can be the failure of mitochondria and cell death.
To help protect themselves from excess protein misfolding and aggregation, cells have evolved signaling pathways that protect mitochondria during stress. These pathways primarily function by increasing the production of mitochondrial "chaperone" molecules that help keep proteins within mitochondria folded properly and protease enzymes that can cut up misfolded and aggregated mitochondrial proteins.
"These signaling pathways that regulate mitochondrial 'proteostasis' mechanisms, as we call them, have so far been poorly characterized in mammalian cells, but on the whole, they seem very important for cellular survival under stress," said Wiseman.
Reducing the Burden
In the new study, Wiseman and members of his laboratory, including first authors Kelly Rainbolt and Neli Atanassova focused on a third mechanism of mitochondrial proteostasis regulation: the reduced "import" of proteins into mitochondria.
"We predicted that reducing the population of newly imported proteins entering mitochondria would reduce the burden on mitochondrial chaperones and proteases during cellular stress," said Rainbolt.