Organization and dynamics of yeast mitochondrial nucleoids

Abstract

Mitochondrial DNA (mtDNA) is packaged by association with specific proteins in compact DNA-protein complexes named mitochondrial nucleoids (mt-nucleoids). The budding yeast Saccharomyces cerevisiae is able to grow either aerobically or anaerobically. Due to this characteristic, S. cerevisiae has been extensively used as a model organism to study genetics, morphology and biochemistry of mitochondria for a long time. Mitochondria of S. cerevisiae frequently fuse and divide, and perform dynamic morphological changes depending on the culture conditions and the stage of life cycle of the yeast cells. The mt-nucleoids also dynamically change their morphology, accompanying morphological changes of mitochondria. The mt-nucleoids have been isolated morphologically intact and functional analyses of mt-nucleoid proteins have been extensively performed. These studies have revealed that the functions of mt-nucleoid proteins are essential for maintenance of mtDNA. The aims of this review are to summarize the history on the research of yeast mt-nucleoids as well as recent findings on the organization of the mt-nucleoids and mitochondrial dynamics.

Autophagy balances mtDNA synthesis and degradation by DNA polymerase POLG during starvation

“…To monitor the spatial distribution and stability of mtDNA within nucleoids in vivo, we used DAPI staining of DNA in combination with fluorescent live-cell imaging ( Williamson and Fennell, 1975 ). WT cells showed a mean of approximately eight discrete mtDNA foci per cell during growth, consistent with previous data ( Chen and Butow, 2005 ; Miyakawa, 2017 ), and maintained this number over 5 d of starvation ( Fig. 1, C–E ).…”

“…In Saccharomyces cerevisiae , the ∼85-kb mitochondrial DNA (mtDNA) encodes for eight proteins, including seven essential respiratory chain subunits, transfer and ribosomal RNAs, and the RNA subunit of RNase P ( Foury et al, 1998 ; Turk et al, 2013 ). The 20–100 mtDNA copies per yeast cell are packaged into multiple dynamic nucleoprotein complexes, termed nucleoids, that remodel in number, distribution, protein composition, and mtDNA content (1–10 copies) in response to metabolic cues ( MacAlpine et al, 2000 ; Kucej et al, 2008 ; Miyakawa, 2017 ). mtDNA replication occurs independently of the nuclear genome throughout the cell cycle but coordinates with mitochondrial division to distribute nucleoids within the network of mitochondria ( Meeusen and Nunnari, 2003 ; Murley et al, 2013 ; Lewis et al, 2016 ).…”

Mitochondrial genetics revisited

“…The discoveries that mtDNA molecules are packaged into protein–DNA complexes, designated nucleoids , in Physarum (Kuroiwa, Kitane, Watanabe, & Kawano, ) and that a HMG ‐like protein is present in yeast mitochondria (Caron, Jacq, & Rouviere‐Yaniv, ) were the first clues to this problem. Subsequent biochemical analyses demonstrated that yeast mitochondrial nucleoids contain a variety of other nuclear‐encoded proteins in addition to the HMG‐like protein encoded by ABF2 (see Table ), Those include the gamma DNA polymerase encoded by MIP1 , the mitochondrial RNA polymerase encoded by RPO41 , the single‐strand DNA‐binding protein encoded by RIM1 , the repair protein encoded by MGM1 , the Hsp10, Hsp60 and Hsp70 chaperonins, and some proteins of the mitochondrial ribosome (Chen & Butow, ; Miyakawa, ). In these complexes, mtDNA molecules are bent by their contact with ABF2 proteins, which, on average, distribute one ABF2 molecule per 15–30 bp of DNA with a preference for GC‐rich sequences.…”

Mitochondrial HMG-Box Containing Proteins: From Biochemical Properties to the Roles in Human Diseases

“…To circumvent this problem, the mtDNA is compacted into condensed nucleo-protein structures called mitochondrial nucleoids (mt-nucleoids) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Considering the diameter of the mt-nucleoids in S. cerevisiae (0.3–0.6 μm) [ 24 ], yeast mtDNA must undergo a compaction of roughly three orders of magnitude.…”