title: Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control.
abstract: Both mitochondria, which are metabolic powerhouses, and telomeres, which help maintain genomic stability, have been implicated in cancer and aging. However, the signaling events that connect these two cellular structures remain poorly understood. Here, we report that the canonical telomeric protein TIN2 is also a regulator of metabolism. TIN2 is recruited to telomeres and associates with multiple telomere regulators including TPP1. TPP1 interacts with TIN2 N terminus, which contains overlapping mitochondrial and telomeric targeting sequences, and controls TIN2 localization. We have found that TIN2 is posttranslationally processed in mitochondria and regulates mitochondrial oxidative phosphorylation. Reducing TIN2 expression by RNAi knockdown inhibited glycolysis and reactive oxygen species (ROS) production and enhanced ATP levels and oxygen consumption in cancer cells. These results suggest a link between telomeric proteins and metabolic control, providing an additional mechanism by which telomeric proteins regulate cancer and aging.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Liuh-Yow
authors.initials: LY
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qinfen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Li
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Luo
authors.forename: Hezhi
authors.initials: H
authors.lastname: Fang
authors.forename: Sok Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Patricia
authors.initials: P
authors.lastname: Yotnda
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
authors.forename: Yidong
authors.initials: Y
authors.lastname: Bai
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D034622:RNA Interference; D020733:RNA, Small Cytoplasmic; D017382:Reactive Oxygen Species / Q000378:metabolism; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C495876:ACD protein, human; D021382:Protein Sorting Signals; D020733:RNA, Small Cytoplasmic; D017382:Reactive Oxygen Species; D000089804:Shelterin Complex; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D000255:Adenosine Triphosphate