RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina

Cell Rep. 2016 Feb 23;14(7):1684-1697. doi: 10.1016/j.celrep.2016.01.039. Epub 2016 Feb 11.


A fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Electron Transport Chain Complex Proteins / genetics*
  • Electron Transport Chain Complex Proteins / metabolism
  • Embryo, Mammalian
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism*
  • Oxidative Stress
  • Photoreceptor Cells, Vertebrate / cytology
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription, Genetic


  • Electron Transport Chain Complex Proteins
  • Repressor Proteins
  • Thap11 protein, mouse
  • Adenosine Triphosphate