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Abstract: FR-PO1007

Light Chain Endocytosis in Renal Proximal Tubular Cells Lead to Impaired Autophagy and Mitophagy

Session Information

  • Onco-Nephrology: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onco-Nephrology

  • 1500 Onco-Nephrology


  • Angel-Korman, Avital, Boston Medical Center, Boston, Massachusetts, United States
  • Spencer, Brian, Boston University, Boston, Massachusetts, United States
  • Igwebuike, Chinaemere, Boston University School of Medicine, Boston, Massachusetts, United States
  • Prokaeva, Tatiana, Boston University, Boston, Massachusetts, United States
  • Wang, Zhiyong, Boston Medical Center, Boston, Massachusetts, United States
  • Borkan, Steven C., Boston Medical Center, Boston, Massachusetts, United States
  • Connors, Lawreen H., Boston University, Boston, Massachusetts, United States
  • Havasi, Andrea, Boston University Medical Center, Boston, Massachusetts, United States

AL amyloidosis is the result of clonal production of amyloidogenic immunoglobulin light chain (LC) proteins, often resulting in renal failure. Although amyloid fibril deposition of LC proteins is a major cause of renal damage in AL amyloidosis, amyloid precursor proteins might also directly impair renal tubular function at the cellular level, independent of fibril formation. Light chains are actively reabsorbed in the proximal tubular epithelial cells (PTECs) by endocytosis and degraded in lysosomes. Lysosomes are also essential for functional autophagy, a process responsible for the removal of damaged mitochondria (mitophagy) and denatured proteins. We hypothesize that LC endocytosis causes PTEC injury by inhibiting autophagy, including mitophagy, resulting in accumulation of dysfunctional mitochondria, that mediates PTEC injury.


Cultured primary PTECs extracted from kidneys of Balb/C mice were exposed in vitro to 6 different LCs purified from patients’ urine. Light chains were derived either from AL amyloid patients with associated nephropathy or from a non-amyloid myeloma patient, as control. Autophagic flux was estimated by immunoblot using the autophagy marker LC3-II, in both bafilomycin treated and untreated cells. Autophagosomes were quantified in live cells using fluorescent microscopy as well as a microplate reader. Mitochondrial respiration and reactive oxygen species production were measured in live cells. Mitochondrial morphology was also assessed using confocal microscopy.


Patient derived LCs caused autophagy inhibition at various levels. Amyloid LC exposed cells accumulated damaged mitochondria with altered mitochondrial function and morphology resulting in increased ROS production.


Dysfunctional autophagy and mitophagy caused by direct cellular toxicity of LCs likely contribute to tubular cell toxicity in AL amyloidosis.


  • NIDDK Support