Quantifying autophagic flux in kidney tissue using structured illumination microscopy

Methods Cell Biol. 2019:153:231-253. doi: 10.1016/bs.mcb.2019.05.004. Epub 2019 Jun 25.

Abstract

Kidney disease is estimated to affect 15% of the world's population. Autophagy is a key homeostatic pathway in eukaryotic cells, which has been linked to numerous pathological states. In the kidney, autophagy has been shown to modulate both acute and chronic injuries. Despite the importance of autophagy in kidney disease, few techniques to precisely monitor autophagic flux in kidney tissue are available. Here we describe an improved technique to quantify autophagic flux using an RFP-GFP-LC3 reporter mouse and super-resolution microscopy. Using structured illumination microscopy, we can resolve individual autophagosomes within kidney tubular cells. We describe the preparation of slides, staining, imaging and data processing. 3D surface rendering is utilized to categorize and quantify autophagosomes by number, size, fluorescence and autophagic flux in response to ischemia.

Keywords: Acute kidney injury; Autophagy; Structured illumination microscopy; Super-resolution microscopy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagosomes / metabolism*
  • Autophagy / immunology*
  • Disease Models, Animal
  • Epithelial Cells
  • Genes, Reporter / genetics
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Histocytological Preparation Techniques / instrumentation
  • Histocytological Preparation Techniques / methods
  • Humans
  • Imaging, Three-Dimensional / instrumentation
  • Imaging, Three-Dimensional / methods*
  • Kidney / cytology
  • Kidney / diagnostic imaging*
  • Kidney / immunology
  • Kidney / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence / instrumentation
  • Microscopy, Fluorescence / methods
  • Reperfusion Injury / diagnostic imaging
  • Reperfusion Injury / immunology
  • Reperfusion Injury / pathology*

Substances

  • Green Fluorescent Proteins