Emerging functional similarities and divergences between Drosophila Spargel/dPGC-1 and mammalian PGC-1 protein.

Subhas Mukherjee,Atanu Duttaroy,Claudette Davis,Mohammed A Basar

doi:10.3389/fgene.2014.00216

Abstract

Peroxisome Proliferator Activated Receptor Gamma Co-activator-1 (PGC-1) is a well-conserved protein among all chordates. Entire Drosophila species subgroup carries a PGC-1 homolog in their genome called spargel/dPGC-1 showing very little divergence. Recent studies have reported that significant functional similarities are shared between vertebrate and invertebrate PGC-1's based on their role in mitochondrial functions and biogenesis, gluconeogenesis, and most likely in transcription and RNA processing. With the help of genetic epistasis analysis, we established that Drosophila Spargel/dPGC-1 affects cell growth process as a terminal effector in the Insulin-TOR signaling pathway. The association between Spargel/dPGC-1 and Insulin signaling could also explain its role in the aging process. Here we provided a further comparison between Spargel/dPGC-1 and PGC-1 focusing on nuclear localization, oxidative stress resistance, and a possible role of Spargel/dPGC-1 in oogenesis reminiscing the role of Spargel in reproductive aging like many Insulin signaling partners. This led us to hypothesize that the discovery of newer biological functions in Drosophila Spargel/dPGC-1 will pave the way to uncover novel functional equivalents in mammals.

Highlights

Homeothermic mammals utilize the Peroxisome Proliferator Activated Receptor Gamma Co-activator 1 (PGC-1) as a thermogenic regulator to protect against excessive cold or excess calorie intake (Puigserver et al, 1998)
In light of the fact that significant functional overlap exists between the three PGC-1 homologs in mice PGC-1α, PGC-1β and PRC, which makes it difficult to tease apart their relative roles in vivo, we propose that the presence of a single Drosophila PGC-1 homolog will provide an enormous advantage to study the function of this essential transcriptional coactivator in an alternate model
Within the last few years, significant functional homologies have surfaced between mammalian PGC-1 and Drosophila Spargel/dPGC-1, which called for a discussion of this topic in greater detail

Summary

Introduction

Homeothermic mammals utilize the Peroxisome Proliferator Activated Receptor Gamma Co-activator 1 (PGC-1) as a thermogenic regulator (maintains body temperature) to protect against excessive cold or excess calorie intake (Puigserver et al, 1998). Following 48 h of starvation, the gut turns thinner and Insulin signaling is reduced, but it imposes no effect on nuclear localization of the Spargel-GFP protein (D).

Results

Conclusion