Molecular chaperones and the biogenesis of mitochondria and peroxisomes

Abstract

A review of the proteinaceous machinery involved in protein sorting pathways and protein folding and assembly in mitochondria and peroxisomes is presented. After considering the various sorting pathways and targeting signals of mitochondrial and peroxisomal proteins, we make a comparative dissection of the protein factors involved in: i) the stabilization of cytosolic precursor proteins in a translocation competent conformation; ii) the membrane import apparatus of mitochondria and peroxisomes; iii) the processing of mitochondrial precursor proteins, and the eventual processing of certain peroxisomal precursor, in the interior of the organelles; and iv) the requirement of molecular chaperones for appropriate folding and assembly of imported proteins in the matrix of both organelles. Those aspects of mitochondrial biogenesis that have developed rapidly during the last few years, such as the requirement of molecular chaperones, are stressed in order to stimulate further parallel investigations aimed to understand the origin, biochemistry, molecular biology and pathology of peroxisomes. In this regard, a brief review of findings from our group and others is presented in which the role of the F1-ATPase alpha-subunit is pointed out as a molecular chaperone of mitochondria and chloroplasts. In addition, data are presented that could question our previous indication that the immunoreactive protein found in the rat liver peroxisomes is due to the presence of the F1-ATPase alpha-subunit.

Targeting and translocation of proteins into the hydrogenosome of the protist Trichomonas: similarities with mitochondrial protein import

“…Many of the properties underlying protein import into the matrix of hydrogenosomes are similar to those previously observed for import of proteins into the mitochondrial matrix (Glick and Schatz, 1991; Cuezva et al ., 1993; Schwarz and Neupert, 1994). Transport into both organelles is dependent on an N‐terminal, cleavable presequence, cytosolic factors, energy in the form of temperature and ATP, and is inhibited by the presence of the protonophore CCCP.…”

An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice

“…UCP1 mRNA upregulation may be one of the effects of mitochondrial biogenesis. It is speculated that molecular chaperones such as HSP72 activate mitochondrial biogenesis (7). It is also known that mitochondrial dysfunction by several stresses can be recovered by activation of heat shock response (4,43,54).…”

Flow cytometry of isolated mitochondria during development and under some pathological conditions

“…It has been clearly demonstrated that during the perinatal period, rat liver mitochondria undergo many significant changes with respect to their structure and function. This process includes mitochondrial proliferation [6,7] whereby the number of mitochondria are increased and organelle differentiation achieved through an exclusive mechanism during which pre‐existing RNA messengers are promptly translated in order to cope with the adaptation to the extra‐uterine life [2,8–11].…”