title: Interfacing mitochondrial biogenesis and elimination to enhance host pathogen defense and longevity.
abstract: Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis and calcium homeostasis, among others. Alterations in mitochondrial activity not only influence individual cell function but also, through non-cell autonomous mechanisms, whole body metabolism, healthspan and lifespan. Energy homeostasis is orchestrated by the complex interplay between mitochondrial biogenesis and mitochondria-selective autophagy (mitophagy). However, the cellular and molecular pathways that coordinate these 2 opposing processes remained obscure. In our recent study, we demonstrate that DCT-1, the Caenorhabditis elegans homolog of the mammalian BNIP3 and BNIP3L/NIX, is a key mediator of mitophagy, and functions in the same genetic pathway with PINK-1 and PDR-1 (the nematode homologs of PINK1 and Parkin respectively) to promote longevity and prevent cell damage under stress conditions. Interestingly, accumulation of damaged mitochondria activates SKN-1 (SKiNhead-1), the nematode homolog of NRF2, which in turn initiates a compensatory retrograde signaling response that impinges on both mitochondrial biogenesis and removal. In this commentary, we discuss the implications of these new findings in the context of innate immunity and aging. Unraveling the regulatory network that governs the crosstalk between mitochondrial biogenesis and mitophagy will enhance our understanding of the molecular mechanisms that link aberrant energy metabolism to aging and disease.
authors.affiliation: Institute of Molecular Biology and Biotechnolog; Foundation for Research and Technology-Hellas Heraklion, Greece; University of Crete ; Heraklion, Greece ; Department of Biology; University of Crete ; Heraklion, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Palikaras
authors.affiliation: Institute of Molecular Biology and Biotechnolog; Foundation for Research and Technology-Hellas Heraklion, Greece; University of Crete ; Heraklion, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Lionaki
authors.affiliation: Institute of Molecular Biology and Biotechnolog; Foundation for Research and Technology-Hellas Heraklion, Greece; University of Crete ; Heraklion, Greece ; Department of Basic Sciences; University of Crete ; Heraklion, Greece.
authors.forename: Nektarios
authors.initials: N
authors.lastname: Tavernarakis
keywords: aging; autophagy; homeostasis; innate immunity; mitochondria; mitophagy; stress