biostudies-literatureBeesetti SNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSBurroughs Wellcome FundAmerican Lebanese Syrian Associated CharitiesNational Institutes of HealthNational Institute of General Medical SciencesSt. Jude Children's Research HospitalNIGMS NIH HHS166453https://www.ebi.ac.uk/biostudies/studies/S-EPMC9844820biostudies-literatureUnknown1868(9)Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. The FA proteins have functions in genome maintenance and in the cytoplasmic process of selective autophagy, beyond their canonical roles of repairing DNA interstrand cross-links. FA core complex proteins FANCC, FANCF, FANCL, FANCA, FANCD2, BRCA1 and BRCA2, which previously had no known direct functions outside the nucleus, have recently been implicated in mitophagy. Although mutations in FANCL account for only a very small number of cases in FA families, it plays a key role in the FA pathophysiology and might drive carcinogenesis. Here, we demonstrate that FANCL protein is present in mitochondria in the control and Oligomycin and Antimycin (OA)-treated cells and its ubiquitin ligase activity is not required for Biochimica et biophysica acta. Molecular basis of diseaseFANCL supports Parkin-mediated mitophagy in a ubiquitin ligase-independent manner.PMC9844820R01 GM132231R21 AI142044R01GM132231Levine BSakurada SMPruett-Miller SMPotts MBBeesetti SSirasanagandla SSumpter RfalseFANCL supports Parkin-mediated mitophagy in a ubiquitin ligase-independent manner.Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. The FA proteins have functions in genome maintenance and in the cytoplasmic process of selective autophagy, beyond their canonical roles of repairing DNA interstrand cross-links. FA core complex proteins FANCC, FANCF, FANCL, FANCA, FANCD2, BRCA1 and BRCA2, which previously had no known direct functions outside the nucleus, have recently been implicated in mitophagy. Although mutations in FANCL account for only a very small number of cases in FA families, it plays a key role in the FA pathophysiology and might drive carcinogenesis. Here, we demonstrate that FANCL protein is present in mitochondria in the control and Oligomycin and Antimycin (OA)-treated cells and its ubiquitin ligase activity is not required for 2022-01-01T00:00:00Z2022 Sep2025-04-04T22:55:13.095Z2025-04-04T22:55:13.095ZS-EPMC98448203564433810.1016/j.bbadis.2022.166453