Molecular Mechanisms of Organelle Biogenesis and Related Metabolic Diseases

Organelle biogenesis is regulated by transcriptional networks that modulate expression of specific genes encoding organellar proteins. Structural and functional specifi city of organelles requires not only the transcription of specifi c genes and translation of resulting mRNAs, but also the transfer of encoded polypeptides to their site of function through signaling peptides. A defect in targeting of proteins to their subcellular site of function may not necessarily prevent biogenesis of the organelle, but would definitely lead to formation of a defective organelle with respect to that specifi c function. Several metabolic diseases are associated with dysfunction or defects in organelle biogenesis; among these, peroxisome biogenesis disorders, mitochondrial biogenesis defects and lysosomal storage disorders are an extensively studied group of genetic diseases where biogenesis of the organelle is compromised either due to a defect in assembly of the organelle itself or impaired import of matrix proteins into the organelle. Recent advances in biochemical and molecular aspects of biogenesis of subcellular organelles have not only unraveled the mechanisms for organization of cellular networks, but have also provided new insights into the development of metabolic diseases that are caused by disruption of organelle biogenesis. This article reviews the molecular mechanisms of biogenesis of mitochondria, lysosomes and peroxisomes in relation to the metabolic diseases of genetic or nongenetic origin. Copyright (C) 2005 S. Karger AG, Basel