Meiotic Cellular Rejuvenation is Coupled to Nuclear Remodeling in Budding Yeast

Autor: Jennifer G Schick, Kent L. McDonald, Jay S Goodman, Keerthana Chetlapalli, Danielle M. Jorgens, Elçin Ünal, Grant A King
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Senescence
Life on Land
QH301-705.5
Macromolecular Substances
Nucleolus
Science
1.1 Normal biological development and functioning
S. cerevisiae
Time-Lapse Imaging
Fluorescence
General Biochemistry
Genetics and Molecular Biology

protein aggregation
Biological Factors
03 medical and health sciences
0302 clinical medicine
Meiosis
Underpinning research
nuclear pore complex
Extrachromosomal DNA
cell biology
Compartment (development)
Biology (General)
nucleolus
quality control
Nuclear pore
030304 developmental biology
Microscopy
0303 health sciences
General Immunology and Microbiology
Chemistry
Prevention
General Neuroscience
Meiosis II
aging
Cell Biology
General Medicine
Cell biology
Microscopy
Fluorescence

Generic Health Relevance
Cytoplasm
Saccharomycetales
Medicine
Biochemistry and Cell Biology
Nucleoporin
030217 neurology & neurosurgery
Research Article
Zdroj: eLife
eLife, Vol 8 (2019)
DOI: 10.1101/602433
Popis: Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and aged cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly, de novo generation of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.
eLife digest The cells of living organisms accumulate damage as they age. Some of this age-associated damage is found around the organism’s DNA. However, when genetic material is passed on during sexual reproduction, newly born offspring avoid inheriting this age-induced damage. This ensures that the progeny are ‘re-set’ with a fresh lifespan that is independent from their parents’ age. A lot of what is known about aging has come from studying budding yeast. Yeast cells can undergo a process called meiosis and divide into four cells known as gametes, which are the equivalents of human sperm and egg. During meiosis, the structure that surrounds the cell’s genetic material – known as the nuclear membrane – remains intact, surrounding the DNA as it separates into four distinct parts. As the cell divides, age-associated factors that were originally present in the parent are not inherited by the gametes, but it remains unclear how this occurs. Now, King, Goodman et al. have investigated this process by attaching fluorescent labels to specific aging factors and tracking how they are distributed inside yeast cells undergoing meiosis. This revealed that age-associated factors were physically sequestered away from the inherited genetic material during meiosis. King, Goodman et al. found that as the nuclear membrane remodeled itself around the genetic material of the four gametes, the damage became confined to a fifth previously unknown membrane-bound compartment. Once outside of the gametes, the aging factors were then selectively destroyed by enzymes released from the parent cell. All cells age, and many of the mechanisms underlying these processes are similar across species and cell types. A better understanding of how cells age, and of the process by which gametes are able to sequester and eliminate age-induced damage, may help guide efforts to combat aging in other cells.
Databáze: OpenAIRE