Cell Biology

Master Controller

Science Signaling  28 Jul 2009:
Vol. 2, Issue 81, pp. ec254
DOI: 10.1126/scisignal.281ec254

Cellular organelles allow the localized regulation of specialized processes. Under certain conditions, such as increased growth, organelles may be required to alter their function. Coordinated regulation of the gene networks required for mitochondrial and endoplasmic reticulum function has been observed. Now, Sardiello et al. have discovered a gene network regulating the lysosome, the major organelle involved in the degradation of internalized macromolecules. Many lysosomal genes were regulated by a single transcription factor, TFEB. TFEB itself can be activated when the lysosome malfunctions and can regulate both the abundance of lysosomes found in the cell and the ability to degrade complex molecules, including a mutant protein that accumulates in patients with Huntington’s disease. These results may have implications for the treatment of human lysosomal storage disorders, which are characterized by the aberrant accumulation of macromolecules causing cellular dysfunction.

M. Sardiello, M. Palmieri, A. di Ronza, D. L. Medina, M. Valenza, V. A. Gennarino, C. Di Malta, F. Donaudy, V. Embrione, R. S. Polishchuk, S. Banfi, G. Parenti, E. Cattaneo, A. Ballabio, A gene network regulating lysosomal biogenesis and function. Science 325, 473–477 (2009).[Abstract] [Full Text]