Mitochondrial calcium release as induced by Hg2+.

Area of Science:

• Mitochondrial biochemistry
• Toxicology
• Cellular physiology

Background:

• Mitochondria play a crucial role in cellular energy metabolism and calcium homeostasis.
• Exposure to heavy metals like mercury can disrupt mitochondrial function.
• Understanding the specific mechanisms of mercury toxicity is vital for cellular health.

Purpose of the Study:

• To investigate the effects of mercuric ions (Hg2+) on calcium (Ca2+) handling in rat kidney mitochondria.
• To elucidate the relationship between mercury binding, mitochondrial membrane potential, and energy status.
• To identify the specific mitochondrial proteins targeted by mercury.

Main Methods:

• Incubation of rat kidney mitochondria with varying concentrations of Hg2+.
• Measurement of intramitochondrial Ca2+ efflux, NAD(P)H/NAD(P) ratio, and mitochondrial membrane potential.
• Quantification of Hg2+ binding to mitochondria.
• Electrophoretic analysis of Hg-labeled mitochondrial proteins using 203Hg2+.

Main Results:

• Hg2+ addition induced significant Ca2+ efflux from mitochondria.
• This efflux was associated with a decreased NAD(P)H/NAD(P) ratio and reduced mitochondrial membrane potential.
• Dithiothreitol enhanced these effects, indicating a role for sulfhydryl groups.
• Hg2+ binding saturated at approximately 9 nmol/mg protein, with 1 nmol/mg sufficient for Ca2+ release in the presence of dithiothreitol.
• 203Hg2+ predominantly bound to mitochondrial proteins of 20 and 30 kDa.

Conclusions:

• Hg2+ disrupts mitochondrial calcium homeostasis by inducing Ca2+ release.
• The observed effects are linked to the reduction of mitochondrial energy status and membrane potential.
• Mercury binding to specific mitochondrial proteins, likely through modification of sulfhydryl groups, mediates Hg2+-induced Ca2+ release.