Abstract

Progressive decline in mitochondrial function is generally considered one of the hallmarks of aging. We have expressed a Ca2+ sensor in the mitochondrial matrix of C. elegans pharynx cells and we have measured for the first time mitochondrial [Ca2+] ([Ca2+]M) dynamics in the pharynx of live C. elegans worms during aging. Our results show that worms stimulated with serotonin display a pharynx [Ca2+]M oscillatory kinetics that includes both high frequency oscillations (up to about 1Hz) and very prolonged “square-wave” [Ca2+]M increases, indicative of energy depletion of the pharynx cells. Mitochondrial [Ca2+] is therefore able to follow “beat-to-beat” the fast oscillations of cytosolic [Ca2+]. The fast [Ca2+]M oscillations kept steady frequency values during the whole worm life, from 2 to 12 days old, but the height and width of the peaks was progressively reduced. [Ca2+]M oscillations were also present with similar kinetics in respiratory chain complex I nuo-6 mutant worms, although with smaller height and frequency than in the controls, and larger width. In summary, Ca2+ fluxes in and out of the mitochondria are relatively well preserved during the C. elegans life, but there is a clear progressive decrease in their magnitude during aging. Moreover, mitochondrial Ca2+ fluxes were smaller in nuo-6 mutants with respect to the controls at every age and decreased similarly during aging.

Highlights

  • Mitochondrial dysfunction constitutes one of the more distinctive characteristics of aging [1,2,3,4,5,6]

  • To monitor mitochondrial [Ca2+], control N2 C. elegans nematodes were microinjected with the plasmid for expression of mitochondrially-targeted YC3.60 in pharynx under the myo-2 promoter

  • Our data show the behavior of C. elegans pharynx [Ca2+]M dynamics for long periods of time, and how it may depend on the worm age and on the presence of a respiratory chain complex I mutation

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Summary

Introduction

Mitochondrial dysfunction constitutes one of the more distinctive characteristics of aging [1,2,3,4,5,6]. The mechanism and functional significance of this progressive mitochondrial alteration is still obscure, because a series of C. elegans mutants with mild mitochondrial alterations have extended lifespan [11]. This apparent paradox - aging is accompanied by mitochondrial alterations, but mitochondrial alterations promote survival - is still unresolved, but probably depends on the activation of specific survival pathways following early mitochondrial alteration [12,13,14,15,16]

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