Opposing function of mitochondrial prohibitin in aging

Marta Artal-Sanz,Nektarios Tavernarakis

doi:10.18632/aging.100246

Marta Artal-Sanz, Nektarios Tavernarakis

Open Access

https://doi.org/10.18632/aging.100246

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Abstract

While specific signalling cascades involved in aging, such as the insulin/IGF-1 pathway, are well-described, the actual metabolic changes they elicit to prolong lifespan remain obscure. Nevertheless, the tuning of cellular metabolism towards maximal survival is the molecular basis of longevity. The eukaryotic mitochondrial prohibitin complex is a macromolecular structure at the inner mitochondrial membrane, implicated in several important cellular processes such as mitochondrial biogenesis and function, molecular signalling, replicative senescence, and cell death. Recent studies inC. elegans have revealed that prohibitin differentially influences aging by moderating fat metabolism and energy production, in response to both intrinsic signalling events and extrinsic cues. These findings indicate that prohibitin is a context-dependent modulator of longevity. The tight evolutionary conservation and ubiquitous expression of prohibitin proteins suggest a similar role for the mitochondrial prohibitin complex during aging in other organisms.

Highlights

Prohibitins are ubiquitous, evolutionarily strongly conserved proteins that localize to mitochondria
Mutations in the only C. elegans transmembrane insulin receptor kinase DAF-2 doubles the lifespan on wild type animals [34,35], and depletion of prohibitins further extends the lifespan of daf-2 mutants by 150% [17]
Prohibitin deficiency extends the lifespan of both nhr-49 and fat-7 mutants [17]. These findings indicate that prohibitin deficiency is beneficial for longevity in situations of altered growth factor signaling, defective mitochondrial function and altered fat metabolism

Summary

Introduction

Prohibitins are ubiquitous, evolutionarily strongly conserved proteins that localize to mitochondria. PHB proteins are expressed at high levels in mammalian proliferating cells, including neoplastic tissues [27,28], underscoring an essential role for prohibitins in regulating mitochondrial metabolism. In C. elegans, depletion of prohibitins by RNAi reduces the lifespan of wild type animals [17], recapitulating the yeast aging phenotype.

Results

Conclusion