Mitochondriolus: assembling mitoribosomes

The ribosome is an ancient ribonucleoprotein machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which are highly modified ribosomes of bacterial descent, specialized for the synthesis of a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. With high-resolution cryo-EM structures of the mitoribosome becoming recently available, the attention is geared towards understanding the mitoribosome biogenetic process and its compartmentalization. Spatial compartmentalization is essential for cytoplasmic ribosome biogenesis. Within the nucleus, the membrane-less nucleolus is organized around the chromosomal regions that contain the ribosomal RNAs (rRNA) genes, and is the site of rRNA transcription and processing, and of ribosome assembly. Nascent rRNA transcripts move away from the DNA template and are detected first in the fibrillar and later in the granular nucleolar components. Subsequently, pre-ribosomal particles are released from the nucleolus to undergo sequential maturation in the nucleoplasm and cytoplasm before they acquire translation competence. Within mitochondria, the genome (mtDNA) and proteins involved in mtDNA maintenance, replication and transcription, form a nucleoprotein complex known as the mitochondrial nucleoid. Hundreds of nucleoids are present per cell, each containing 1-5 mtDNA molecules. Recent data has indicated that the assembly of mitochondrial ribosomes occurs near the nucleoid [1], at least partially in bromouridine (BrU)-positive RNA foci that form a compartment known as the mtRNA granule [2-5]. We have renamed this compartment as the mitochondriolus, given that it has features equivalent to the nucleolus [4]. The stages of mitoribosome biogenesis occurring at the nucleoid or at the mitochondriolus are a source of current debate in the field. Formaldehyde cross-linking performed to determine the nucleoid proteins that are in close contact with the mtDNA, led to a model for a layered structure of nucleoids in which replication and transcription occur in the central core, whereas RNA processing and translation may occur in the peripheral region. Affinity purification of known mammalian nucleoid components followed by mass spectrometry identified proteins involved in mtDNA metabolism and additionally many mitoribosome proteins (MRPs) and translation factors, indicating an intimate association among nucleoids, components of the mitochondrial translation machinery and foci containing ribonucleoprotein complexes. Supporting this view, the absence of MPV17L2, a protein required for mitoribosome assembly whose stability depends on mtDNA, induces the trapping of mitoribosome small subunit (mtSSU) proteins in enlarged nucleoids [6]. This has suggested the hypothesis that the mtSSU could be assembled at the nucleoid, …