9 research outputs found
Parallel Structural Evolution of Mitochondrial Ribosomes and OXPHOS Complexes
The five macromolecular complexes that jointly mediate oxidative
phosphorylation (OXPHOS) in mitochondria consist of many more subunits than
those of bacteria, yet, it remains unclear by which evolutionary mechanism(s)
these novel subunits were recruited. Even less well understood is the
structural evolution of mitochondrial ribosomes (mitoribosomes): while it was
long thought that their exceptionally high protein content would physically
compensate for their uniquely low amount of ribosomal RNA (rRNA), this
hypothesis has been refuted by structural studies. Here, we present a cryo-
electron microscopy structure of the 73S mitoribosome from Neurospora crassa,
together with genomic and proteomic analyses of mitoribosome composition
across the eukaryotic domain. Surprisingly, our findings reveal that both
structurally and compositionally, mitoribosomes have evolved very similarly to
mitochondrial OXPHOS complexes via two distinct phases: A constructive phase
that mainly acted early in eukaryote evolution, resulting in the recruitment
of altogether approximately 75 novel subunits, and a reductive phase that
acted during metazoan evolution, resulting in gradual length-reduction of
mitochondrially encoded rRNAs and OXPHOS proteins. Both phases can be well
explained by the accumulation of (slightly) deleterious mutations and
deletions, respectively, in mitochondrially encoded rRNAs and OXPHOS proteins.
We argue that the main role of the newly recruited (nuclear encoded)
ribosomal- and OXPHOS proteins is to provide structural compensation to the
mutationally destabilized mitochondrially encoded components. While the newly
recruited proteins probably provide a selective advantage owing to their
compensatory nature, and while their presence may have opened evolutionary
pathways toward novel mitochondrion-specific functions, we emphasize that the
initial events that resulted in their recruitment was nonadaptive in nature.
Our framework is supported by population genetic studies, and it can explain
the complete structural evolution of mitochondrial ribosomes and OXPHOS
complexes, as well as many observed functions of individual proteins
BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins
Release of apoptogenic proteins such as cytochrome c from mitochondria is regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic BH3-only proteins activating Bax and Bak. Current models assume that apoptosis induction occurs via the binding and inactivation of anti-apoptotic Bcl-2 proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze apoptosis induction by the BH3-only protein BimS. Regulated expression of BimS in epithelial cells was followed by its rapid mitochondrial translocation and mitochondrial membrane insertion in the absence of detectable binding to anti-apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of Bax and apoptosis. Mutational analysis of BimS showed that mitochondrial targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis induction. In yeast, BimS enhanced the killing activity of Bax in the absence of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only protein can occur through a process that is independent of anti-apoptotic Bcl-2 proteins but requires mitochondrial targeting
Ribosome-binding Proteins Mdm38 and Mba1 Display Overlapping Functions for Regulation of Mitochondrial Translation
Here we report that Mdm38 and Mba1 display overlapping functions in mitochondrial protein expression. Both Mdm38 and Mba1 interact with mitochondrial ribosomes and are required for translation of COX1 and cytochrome b mRNAs