Sci. Aging Knowl. Environ., 7 January 2004
Vol. 2004, Issue 1, p. nf2
[DOI: 10.1126/sageke.2004.1.nf2]

NEWS FOCUS

Picky Eater

Gluttonous cellular recycler hungers for damaged proteins

R. John Davenport

http://sageke.sciencemag.org/cgi/content/full/2004/1/nf2

SAN FRANCISCO, CALIFORNIA--In a restaurant or a cell, a voracious eater can still have refined tastes. A cellular hog is even more discriminating than previously thought, according to work presented here 14 December at the American Society for Cell Biology annual meeting. The protein-digesting organelle known as the lysosome prefers oxidized molecules, according to the study. Because this cellular component loses its appetite with age, the new study suggests one way that marred proteins accumulate over time.

Cells recycle their parts to regulate biochemical processes and to demolish defective molecules. In one disposal system, the lysosome engulfs whole sections of a cell's insides and dissolves them, a mechanism known as autophagy. With age, lysosome activity falters, and proteins damaged by noxious compounds called reactive oxygen species (ROS) stack up. To check for a connection between these trends, cell biologists Christopher Christian and Ana Maria Cuervo of Albert Einstein College of Medicine in New York City investigated whether lysosomes target oxidized proteins.

The researchers treated mice with the herbicide paraquat, which spurs cells to spew ROS, and isolated lysosomes from the animals' livers. Organelles from the treated animals harbored more oxidized proteins than did samples from controls. Moreover, the lysosomes contained some but not all scarred proteins found in a cell's innards, suggesting that the trash disposers didn't pick them up by chance. To test whether the organelles prefer spoiled molecules to healthy ones, the team treated mice with oxidants, then mixed some of the rodents' proteins with lysosomes. The organelles gulped the damaged molecules five times faster than they did proteins from untreated animals. Additional tests showed that lysosomes from treated rodents munched an unoxidized protein more readily than did organelles from untreated mice. Together the results suggest that lysosomes selectively swallow injured proteins and that oxidative stress enhances this capability.

Lysosomes take up proteins by multiple routes, including one in which they munch individual proteins. In this specialized form of autophagy, proteins called chaperones escort the condemned molecules to a receptor protein embedded in lysosome membranes. The researchers determined whether oxidative stress activates this mechanism. Feeding animals paraquat elevated the amounts of the receptor. The results suggest that the chaperone-mediated autophagy (CMA) system ushers damaged proteins into lysosomes. To test that idea, the researchers now want to investigate whether blocking this junk-disposal pathway in animals leaves lysosomes hungry.

Despite CMA, "people usually think of lysosomes as not selective," says cell biologist He-Jin Lee of the Parkinson's Institute in Sunnyvale, California. This study establishes that they process damaged proteins, and "that's novel," he says. In other research presented at the meeting, Lee and colleagues revealed that lysosomes break up toxic aggregates of a protein implicated in Parkinson's disease. CMA might be responsible for that effect, Lee adds, although he favors other forms of autophagy. Helping old lysosomes keep their refined taste for worn-out proteins might alleviate some of the pitfalls of aging.


January 7, 2004
  1. C. J. Christian and A. Cuervo, Participation of chaperone-mediated autophagy in the selective degradation of oxidized proteins. American Society for Cell Biology 43rd Annual Meeting, 13-17 December 2003, San Francisco, California. [Meeting Web Site]
  2. H. Lee, F. Khoshaghideh, S. Patel, S. Lee, Clearance of {alpha}-synuclein oligomeric intermediates via the lysosomal degradation pathway. American Society for Cell Biology 43rd Annual Meeting, 13-17 December 2003, San Francisco, California. [Meeting Web Site]
Citation: R. J. Davenport , Picky Eater. Sci. Aging Knowl. Environ. 2004 (1), nf2 (2004).








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