Connecting variability in global transcription rate to mitochondrial variability

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Genetically identical eukaryotic cells exhibit significant cell-to-cell variability in gene expression.
• The origins of this transcriptional variation remain incompletely understood.
• Variability in cellular mitochondrial mass and transcription rates are observed.

Purpose of the Study:

• To investigate the origins of cell-to-cell variability in gene expression.
• To determine the relationship between energy metabolism and transcription rate.
• To identify factors influencing transcription rate variability.

Main Methods:

• Cell fusion experiments to assess diffusible factors.
• In vitro studies on transcription rate dependence on nucleotide triphosphates (NTPs), particularly ATP.
• In vivo perturbation of nutrient and ATP levels.
• Analysis of mitochondrial mass, membrane potential, and antioxidant effects.
• Stochastic segregation analysis of mitochondria in daughter cells.

Main Results:

• Transcription rate variability is linked to cellular mitochondrial mass and membrane potential.
• Transcription rate is sensitive to intracellular ATP concentration but not other NTPs.
• Antioxidants modulate transcription rate variability.
• Stochastic segregation of mitochondria at cell division causes variability in mitochondrial content.
• Daughters with lower mitochondrial mass exhibit longer cell cycles.

Conclusions:

• Cellular energy metabolism, particularly ATP levels and mitochondrial content, is a key determinant of transcription rate variability.
• Variability in mitochondrial mass, arising from stochastic segregation, influences cell cycle progression.
• A direct link exists between energy metabolism fluctuations and gene transcription rates in eukaryotic cells.