Conserved AAA-ATPase Afg1 mediates mitochondrial fidelity and cellular healthspan
Edward M. Germany1, Nataliya Zahayko1, Iryna Bohovych1, Jennifer L. Fox2, Veena Prahlad3, Oleh Khalimonchuk1,4*
1Department of Biochemistry, 4Redox Biology Center, University of Nebraska, Lincoln, NE,
2Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC, 3Department of Biology, Aging Mind and Brain Initiative, University of Iowa, Iowa City, IA
Mitochondrial functions are critical for cellular physiology. Several conserved mechanisms are in place to maintain mitochondrial fidelity; however, many of the molecular details and components involved in these activities remain uncharacterized. Here we identify a novel role for the conserved mitochondrial AAA-ATPase Afg1 (LACE1 or AFG1L in higher eukaryotes) in mediating mitochondrial matrix proteostasis during aging and in response to various cellular insults.
We extend these observations to a metazoan system by showing that the loss of the Afg1 ortholog LACE-1 in the roundworm Caenorhabditis elegans is associated with reduced lifespan and impeded stress tolerance. We further show that LACE-1-deficient animals exhibit impaired mitochondrial proteostasis in motor neurons and display altered behavioral plasticity. Our findings reveal a previously unrecognized, evolutionarily conserved role for Afg1 in mitochondrial surveillance and cellular and organismal healthspan.
Funding: NIH grants GM103335, GM108975 (O.K.); T32 GM107001-01A1 (E.M.G.)