H. Arlt et al., THE FORMATION OF RESPIRATORY-CHAIN COMPLEXES IN MITOCHONDRIA IS UNDERTHE PROTEOLYTIC CONTROL OF THE M-AAA PROTEASE, EMBO journal (Print), 17(16), 1998, pp. 4837-4847
Yta10p (Afg3p) and Yta12p (Rcal1p), members of the conserved AAA famil
y of ATPases, are submits of the mitochondrial m-AAA protease, an inne
r membrane ATP-dependent metallopeptidase. Deletion of YTA10 or YTA12
impairs degradation of nonassembled inner membrane proteins and assemb
ly of respiratory chain complexes, Mutations of the proteolytic sites
in either YTA10 or YTA12 have been shown to inhibit proteolysis of mem
brane-integrated polypeptides but not the respiratory competence of th
e cells, suggesting additional activities of Yta10p and Yta12p. Here w
e demonstrate essential proteolytic functions of the m-AAA protease in
the biogenesis of the respiratory chain. Cells harbouring proteolytic
ally inactive forms of both Yta10p and Yta12p are respiratory deficien
t and exhibit a pleiotropic phenotype similar to Delta yta10 and Delta
yta12 cells, They show deficiencies in expression of the intron-conta
ining mitochondrial genes COX1 and COB, Splicing of COX1 and COB trans
cripts is impaired in mitochondria lacking m-AAA protease, whilst tran
scription and translation can proceed in the absence of Yta10p or Yta1
2p, The function of the m-AAA protease appears to be confined to intro
ns encoding mRNA maturases. Our results reveal an overlapping substrat
e specificity of the subunits of the m-AAA protease and explain the im
paired assembly of respiratory chain complexes by defects in expressio
n of intron-containing genes in mitochondria lacking m-AAA protease.