Open AccessCaenorhabditis elegans ATPase inhibitor factor 1 (IF1) MAI-2 preserves the mitochondrial membrane potential (Δψm) and is important to induce germ cell apoptosis
Author(s) -
Laura Paulette Fernández-Cárdenas,
Emmanuel Villanueva-Chimal,
Laura S. Salinas,
Concepción José-Nuñez,
Marietta Tuena de Gómez Puyou,
Rosa E. Navarro
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0181984
Subject(s) - caenorhabditis elegans , biology , mitochondrion , microbiology and biotechnology , atp synthase , inhibitor protein , cytoplasm , atpase , biochemistry , gene , enzyme
When the electrochemical proton gradient is disrupted in the mitochondria, IF 1 (Inhibitor Factor-1) inhibits the reverse hydrolytic activity of the F 1 F o -ATP synthase, thereby allowing cells to conserve ATP at the expense of losing the mitochondrial membrane potential (Δ ψ m ). The function of IF 1 has been studied mainly in different cell lines, but these studies have generated contrasting results, which have not been helpful to understand the real role of this protein in a whole organism. In this work, we studied IF 1 function in Caenorhabditis elegans to understand IF 1 ´s role in vivo . C . elegans has two inhibitor proteins of the F 1 F o -ATPase, MAI-1 and MAI-2. To determine their protein localization in C . elegans , we generated translational reporters and found that MAI-2 is expressed ubiquitously in the mitochondria; conversely, MAI-1 was found in the cytoplasm and nuclei of certain tissues. By CRISPR/Cas9 genome editing, we generated mai-2 mutant alleles. Here, we showed that mai-2 mutant animals have normal progeny, embryonic development and lifespan. Contrasting with the results previously obtained in cell lines, we found no evident defects in the mitochondrial network, dimer/monomer ATP synthase ratio, ATP concentration or respiration. Our results suggest that some of the roles previously attributed to IF 1 in cell lines could not reflect the function of this protein in a whole organism and could be attributed to specific cell lines or methods used to silence, knockout or overexpress this protein. However, we did observe that animals lacking IF 1 had an enhanced Δ ψ m and lower physiological germ cell apoptosis. Importantly, we found that mai-2 mutant animals must be under stress to observe the role of IF 1 . Accordingly, we observed that mai-2 mutant animals were more sensitive to heat shock, oxidative stress and electron transport chain blockade. Furthermore, we observed that IF 1 is important to induce germ cell apoptosis under certain types of stress. Here, we propose that MAI-2 might play a role in apoptosis by regulating Δ ψ m . Additionally, we suggest that IF 1 function is mainly observed under stress and that, under physiological conditions, this protein does not play an essential role.