Per Stromhaug

Assistant Professor of Biological Sciences

PhD, 1997 University of Oslo, Norway

stromhaugpe@missouri.edu
573-882-3970
423 Tucker Hall

Research description

In a society obsessed with growth and gain we often seem to overlook the importance of a healthy equilibrium where growth is balanced by a controlled turnover. Yet, we spend most of our lives as adults trying to avoid accumulation of more mass. An adult human being is entirely dependent on certain cells to grow and divide in a controlled manner to replace old and dying cells, while other cells cannot be replaced and their death may cause detrimental defects and diseases. In order to stay healthy and avoid unwanted cell death, all cells need to have a steady turnover of aging and defective cell components. They also need to modify their contents according to the clues given to them from the surrounding cells and environment, for example during embryogenesis and differentiation and upon nutritional limitations. The process by which the cell removes pieces of itself is called autophagy, which translates into “self-eating”.

Autophagy is a highly regulated process where the cell decides to sequester certain intracellular cell components into vesicles called autophagosomes. The autophagosome delivers the engulfed material to the lysosome where all macromolecules are hydrolyzed into monomeric building blocks. These building blocks are returned to the cytosol and can be incorporated into new macromolecules. In this way, the cells can recycle old components as well as respond to nutritional stress by sacrificing a small portion of itself in order to build new cell components needed to survive the stress situation. Degradation by autophagy can counterbalance cell growth and it has been found that many cancer cells therefore have eliminated this growth control pathway. Furthermore, autophagy is used by the cell to fight pathogenic bacteria that invade the cell. These are taken up by autophagy and destroyed. While multicellular organisms are dependent on autophagy for survival, too much autophagy may be detrimental to the cell. In fact, autophagy is used by cells under certain circumstances to commit controlled suicide while in other instances uncontrolled cell death by autophagy may cause death of nerve cells and neurological disorders. It is therefore obvious that autophagy must be tightly regulated – too much may be just as bad as too little!

If we shall be able to manipulate autophagy in order to improve human health, it is essential that we learn more about all aspects of the process. It is still not clear how the intracellular components are taken up into the autophagosome or how the process is controlled. Nor do we know all the problems associated with improperly regulated autophagy. In our lab, we are trying to shed light on the molecular mechanisms governing when and how autophagosomes form. We are trying to determine the role autophagy proteins play in assembling membranes together around cytosolic components by using in vivo and in vitro experiments. Many of the experiments are performed using various yeasts as a model systems. Yeast cells, just like mammalian cells, are dependent on autophagy for survival upon environmental changes and nutritional limitations. The yeast S. cerevisiae is furthermore using autophagy for delivery of the protease Aminopeptidase I (Ape1) to the vacuole. This specialized form of autophagy is called the Cvt pathway and is a convenient model system for the study of the molecular events taking place during the formation of autophagic vesicles. The Cvt pathway utilizes the same proteins and molecular mechanisms as autophagy in yeast cells and higher eukaryotes. We are currently focusing on yeast proteins and their mammalian counterparts that bind to, modify and target the membrane that will assemble into autophagosomes.

Selected publications

Chang, T., Schroder, L.A., Thompson, J.M., Klocman, A.S., Tomasini, A.J., Strømhaug, P.E. and Dunn, Jr., W.A. 2005. PpATG9 encodes a novel membrane protein that traffics to vacuolar membranes which sequester peroxisomes during pexophagy in Pichia pasoris. Mol. Biol. Cell, 16: 4941-4953.

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, 15, 3553-66

F. Reggiori, K.A.,Tucker, Strømhaug, P.E., D.J., Klionsky. 2004. Atg1- Atg3 complex regulates Atg9 and Atg 23 retrieval transport from the pre-autophagosomal structure. Dev. Cell, 6: 79-90.

Strømhaug, P.E., A. Bevan and W.A. Dunn, Jr. 2001. GSA11 encodes a unique 208 kDa protein required for pexophagy and autophagy in Pichia pastoris. J. Biol. Chem. 276, 42422-42435.

Strømhaug, P.E., and D.J. Klionsky 2001. Approaching the molecular mechanism of autophagy. Traffic 2, 524-531.

Strømhaug, P.E., Berg, T.O., Fengsrud, M. and Seglen, P.O. 1998. Purification and characterization of autophagosomes from rat hepatocytes. Biochem. J. 335, 217-24.

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