Stimulation of the Synthesis of Inner Mitochondrial Membrane Proteins in Rat Liver by Cuprizone

Abstract

During the past 5 years, an increasing body of evidence has confirmed earlier suggestions favoring the autonomy of the mitochondrial protein synthesizing machinery based on the ability of isolated organelles to incorporate amino acids into protein (1-3). Rather paradoxically, the discovery of mitochondrial DNA, RNA, polymerases, ribosomes, tRNA, etc., was concomitant with a progressive decrease in what was considered to be the degree of autonomy of mitochondrial replication. The initial evaluation of the very restricted information content of mitochondrial DNA (4) and the demonstration that cytochrome c is coded by the nuclear genome (5) was soon followed by proof of the synthesis of this mitochondrial protein by cytoplasmic ribosomes (6,7). Other proteins, such as those of mitochondrial ribosomes (8,9), outer membrane proteins (10), cytochrome oxidase (11,12), cytochrome b (12), and ATPase (13), were later shown to be synthesized outside the organelle. A recent assessment of the amount of protein synthesized by endogenous mitochondrial activity (14) implies that 90% of the mitochondrial proteins are, in fact, manufactured by 80S ribosomes. Apparently, the organeile is only able to synthesize some large insoluble proteins (11) and perhaps peptides (15).