%0 Journal Article
%T Targeting Metabolism and Autophagy in the Context of Haematologic Malignancies
%A Versha Banerji
%A Spencer B. Gibson
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/595976
%X Autophagy is a cellular process that maintains the homeostasis of the normal cell. It not only allows for cell survival in times of metabolic stress with nutrient recycling but also is able to lead to cell death when required. During malignant transformation the cell is able to proliferate and survive. This is due to altered cell metabolism and the presence of altered genetic changes that maintain the cell survival. Metabolism was considered an innocent bystander that was a consequence of the increased nutrient requirement for the survival and proliferation of haematological malignancies. The interdependency of metabolism and cellular mechanisms such as autophagy are becoming more evident and important. This interdependence contributes to increased cancer progression and drug resistance. In this paper we aim to discuss autophagy, how it pertains to metabolism in the context of hematologic malignancies, and the implications for therapy. 1. Introduction Autophagy was first described in the 1960s but its importance in various physiological conditions in addition to the basic molecular understanding of autophagy has only come into focus in the last decade. The word autophagy is derived from Greek: auto, meaning ˇ°selfˇ± and phagy, ˇ°to eat.ˇ± This term was coined due to the process by which cellular components are degraded through the lysosomal enzymatic pathway providing a cell with essential amino acids, nucleotides, and fatty acids that enable production of the elements required for energy and macromolecule production [1, 2]. Normal cells engage in autophagy as a means to survive disruptions in nutrient and growth factor availability. It also serves to eliminate damaged organelles and proteins to prevent accumulation. This prevents them from becoming toxic to the cell. If autophagy is prolonged to a point where normal cell function is compromised, cells undergo cell death either through apoptosis or by autophagy itself. One of the main inducers of autophagy is metabolic stress, and understanding the relationship between autophagy and metabolism could lead to better therapeutic strategies in treatment of haematological malignancies. 2. Regulation of Autophagy Autophagy is characterized by cytoplasmic constituents sequestered into double-membraned vacuoles called autophagosomes. Autophagosomes then fuse with lysosomes (autolysosomes). Autolysosomes degrade cellular components releasing required nutrients to the cell. The regulation of autophagosome and autolysosome structures requires both positive and negative signaling pathways. The discovery in yeast of
%U http://www.hindawi.com/journals/ijcb/2012/595976/