Sirtuin activation: a role for plasma membrane in the cell growth puzzle
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Published on: February 27, 2016
Frederick L Crane1, Plácido Navas, Hans Low
1Biology Department, Purdue University, West Lafayette, IN, USA.
Abstract:
For more than 20 years, the observation that impermeable oxidants can stimulate cell growth has not been satisfactorily explained. The discovery of sirtuins provides a logical answer to the puzzle. The NADH-dependent transplasma membrane electron transport system, which is stimulated by growth factors and interventions such as calorie restriction, can transfer electrons to external acceptors and protect against stress-induced apoptosis. We hypothesize that the activation of plasma membrane electron transport contributes to the cytosolic NAD(+) pool required for sirtuin to activate transcription factors necessary for cell growth and survival.
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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