Sirtuin activation: a role for plasma membrane in the cell growth puzzle

Frederick L Crane1, Plácido Navas, Hans Low

  • 1Biology Department, Purdue University, West Lafayette, IN, USA.

Insights

Impermeable oxidants stimulate cell growth by activating plasma membrane electron transport. This process increases the NAD(+) pool, enabling sirtuins to promote cell growth and survival.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • The mechanism by which impermeable oxidants stimulate cell growth has remained unexplained for over two decades.
  • Sirtuins, a class of proteins, have emerged as key players in cellular regulation and longevity.

Purpose of the Study:

  • To explain the long-standing puzzle of how impermeable oxidants stimulate cell growth.
  • To elucidate the role of plasma membrane electron transport and sirtuins in cell growth and survival.

Main Methods:

  • Investigating the NADH-dependent transplasma membrane electron transport system.
  • Examining the impact of growth factors and calorie restriction on this system.
  • Analyzing the cytosolic NAD(+) pool and its relation to sirtuin activity.

Main Results:

  • The transplasma membrane electron transport system transfers electrons to external acceptors, offering protection against apoptosis.
  • Activation of this system is linked to increased cytosolic NAD(+) levels.
  • This elevated NAD(+) pool is crucial for sirtuin-mediated activation of transcription factors.

Conclusions:

  • The activation of plasma membrane electron transport provides a mechanism for oxidant-induced cell growth.
  • This pathway contributes to cellular survival by modulating the NAD(+) pool for sirtuin function.

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