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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
06:26

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

Mitochondria in Ca2+ signaling and apoptosis

S S Smaili1, Y T Hsu, R J Youle

  • 1Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4495, USA.

Journal of Bioenergetics and Biomembranes
|January 5, 2002
PubMed

Insights

Mitochondria regulate cellular calcium (Ca2+) signals, impacting cell life and death. Mitochondrial calcium overload can trigger cell death pathways, involving the permeability transition pore and apoptosis signaling.

Area of Science:

  • Cell Biology
  • Mitochondrial Physiology
  • Calcium Signaling

Background:

  • Cellular calcium (Ca2+) signals are vital for physiological processes, cell injury, and programmed cell death.
  • Mitochondria critically regulate cytosolic Ca2+ ([Ca2+]c) through various transport mechanisms, influencing Ca2+-sensitive cellular functions.

Purpose of the Study:

  • To elucidate the role of mitochondrial Ca2+ transport and the permeability transition pore (PTP) in cell death.
  • To discuss the involvement of the PTP in apoptosis signaling pathways, including the Bcl-2 family of proteins.

Main Methods:

  • Review and discussion of established mechanisms of mitochondrial Ca2+ transport.
  • Analysis of the role of PTP opening in mitochondrial membrane potential disruption and cell death.
  • Examination of the interplay between mitochondrial Ca2+ handling, apoptosis signaling, and Bcl-2 family proteins.

Main Results:

  • Mitochondria regulate [Ca2+]c via uptake and release pathways, including the PTP, uniporter, and Na+/Ca2+ exchanger.
  • Cellular Ca2+ overload leads to mitochondrial Ca2+ uptake, PTP opening, loss of mitochondrial membrane potential (delta(psi)m), and cell death.
  • Mitochondrial dysfunction, including delta(psi)m collapse and cytochrome c release, is a key event in apoptosis, preceding caspase activation and DNA fragmentation.

Conclusions:

  • Mitochondrial Ca2+ regulation is central to cell survival and death.
  • The PTP is a critical mediator of cell death during Ca2+ overload and apoptosis.
  • Understanding mitochondrial Ca2+ dynamics and PTP function offers insights into cell death mechanisms and potential therapeutic targets.

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