Daniel J. Klionsky, Ph.D.

Professor, Biological Chemistry

A.B., University of California, Los Angeles
Ph.D., Stanford University
Postdoctoral, California Institute of Technology

Research Profile

Like many people, we are interested in understanding the molecular basis of human diseases with an ultimate goal of prevention and/or treatment. Animal cells, however, are difficult to work with experimentally. In contrast, yeast cells provide a relatively simple model system, and studies carried out in yeast are typically applicable to higher eukaryotes. We are interested in the areas of protein targeting and organelle biogenesis. In the past few years, our studies have led us into the area of autophagy. Autophagy is an essential process that allows cell survival under certain stress conditions, yet the molecular details of this process are only now becoming understood. In brief, a cytosolic double membrane vesicle (autophagosome) engulfs portions of cytoplasm. Subsequent fusion with the vacuole (the equivalent of the lysosome) delivers the cargo to the lumen where it can be broken down and recycled. This process plays a normal role in the development of eukaryotic organisms, and is thought to be involved in lifespan extension. On the other hand, autophagic dysfunction is associated with various diseases in humans including cancer and neurodegenerative diseases such as Parkinson's and Alzheimer's disease.

Recent analyses of the autophagy gene products (approximately 27 at present) have begun to provide insight into the molecular mechanism for autophagy and a related biosynthetic process called the cytoplasm to vacuole targeting (Cvt) pathway. For example, both processes require the action of two ubiquitin-like proteins, Atg8 and Atg12, which may act in forming a transient coat that allows formation of the autophagosome. The Cvt pathway may be viewed as a type of specific autophagy. Accordingly, the Cvt pathway, along with other processes including peroxisome degradation, requires components that confer specificity. These proteins, such as Atg11 and Atg19, play roles in cargo recognition and packaging. Continued studies will focus on determining protein interactions, mapping functional domains, reconstituting the sequestration process in vitro and carrying out structural analyses to complete our understanding of this medically relevant process that is fundamental to eukaryotic cell physiology.

Awards

2003 Nat Sci. Foundation Director’s Award for Distinguished Teaching Scholars
2006 Reviewer for John Simon Guggenheim Memorial Foundation
2006 National Academies Education Mentor in the Life Sciences

PubMed Search Term : klionsky dj

Publications

Abeliovich, H., C. Zhang, W.A. Dunn, Jr., K.M. Shokat and D.J. Klionsky. 2003. Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. Mol. Biol. Cell, 14: 477-490.

Reggiori, F., C.-W. Wang, P.E. Stromhaug, T. Shintani and D.J. Klionsky. 2003. Vps51 is part of the yeast Vps Fifty-three tethering complex essential for retrograde traffic from the early endosome and Cvt vesicle completion.  J. Biol. Chem. 278: 5009-5020.

Tucker, K.A., F. Reggiori, W.A. Dunn Jr. and D.J. Klionsky. 2003. Atg23 is essential for the cytoplasm to vacuole targeting pathway and efficient autophagy but not pexophagy. J. Biol. Chem., 278: 48445-48452.

Wang, C.-W., P.E. Stromhaug, E.J. Kauffman, L.S. Weisman and D.J. Klionsky. 2003. Yeast homotypic vacuole fusion requires the Ccz1-Mon1 complex during the tethering/docking stage. J. Cell Biol., 163: 973-985.

Reggiori, F., K.A. Tucker, P.E. Stromhaug and D.J. Klionsky. 2004. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev. Cell, 6: 79-90. PMID: 14723849

Levine, B. and D.J. Klionsky. 2004. Development by Self-Digestion: Molecular mechanisms and biological functions of autophagy. Dev. Cell, 6: 463-477. PMID: 15068787

Reggiori, F., C.-W. Wang, U. Nair, H. Abeliovich and D.J. Klionsky. 2004. Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Mol. Biol. Cell, 15: 2189-2204. PMID: 15004240

Budovskaya, Y.V., J.S. Stephan, F. Reggiori, D.J. Klionsky and P.K. Herman. 2004. The Ras/PKA signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. J. Biol. Chem. 279: 20663-20671

Shintani, T. and D.J. Klionsky. 2004. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J. Biol. Chem., 279: 29889-29894. PMID: 15138258

Strømhaug, P.E., F. Reggiori, J. Guan, C.-W. Wang and D.J. Klionsky. 2004. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Mol. Biol. Cell, in press. PMID: 15155809