Related Experiment Video

Updated: Oct 8, 2025

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

9.9K

Mosaic PKHD1 in Polycystic Kidneys Caused Aberrant Protein Expression in the Mitochondria and Lysosomes

Chengxian Xu1, Chenxi Yang2, Qing Ye1

  • 1Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, China.

Frontiers in Medicine
|January 3, 2022
PubMed

Insights

Autosomal recessive polycystic kidney disease (ARPKD) is a severe genetic kidney disorder. This study reveals PKHD1 gene variants and mosaicism in affected families, highlighting mitochondrial and lysosomal dysfunction in ARPKD pathophysiology.

Area of Science:

  • Genetics
  • Molecular Biology
  • Pathology

Background:

  • Autosomal recessive polycystic kidney disease (ARPKD) is a severe genetic renal cystic disease.
  • The genetic causes, pathological features, and mechanisms of ARPKD remain incompletely understood.
  • The polycystic kidney and hepatic disease 1 (PKHD1) gene is the primary genetic cause of ARPKD.

Purpose of the Study:

  • To investigate the genetic basis and pathological mechanisms of ARPKD in a family with affected siblings.
  • To characterize the molecular and cellular alterations in ARPKD patients with PKHD1 variants.
  • To explore the role of exosome proteomics in understanding ARPKD pathophysiology.

Main Methods:

  • Genetic analysis of a family with ARPKD to identify PKHD1 variants.
  • Pathological characterization of kidney biopsy samples using microscopy.
  • Exosome isolation from patient urine and proteomic analysis.
  • Analysis of mitochondrial and lysosomal protein expression and cellular morphology.

Main Results:

  • Identified biallelic PKHD1 variants in siblings, including paternal mosaicism for one variant.
  • Pathology revealed predominant proximal tubule dilation, defective ciliogenesis, and impaired cell junctions.
  • Exosome proteomics showed significant alterations in mitochondrial and lysosomal proteins, with downregulated OXPHOS and upregulated glycolysis.
  • Increased abundance of specific lysosomal proteins, including sulfamidase, was observed in patient exosomes.
  • Mutant tubular epithelial cells displayed swollen mitochondria and abundant lysosomes.

Conclusions:

  • PKHD1 deficiency leads to significant alterations in mitochondrial and lysosomal function, contributing to ARPKD pathophysiology.
  • Exosome proteomics offers valuable insights into the molecular mechanisms of ARPKD.
  • PKHD1 mosaicism should be considered during genetic testing for ARPKD.

Keywords:
ARPKDPKHD1exosomelysosomemitochondriamosaicism

More Related Videos

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring07:35

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Published on: June 23, 2015

11.6K
Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease12:47

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Published on: February 3, 2012

38.7K

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
Nephrons01:10

Nephrons

The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
3.7K
Overview of Protein Metabolism01:21

Overview of Protein Metabolism

Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
2.2K
Inborn Errors of Metabolism01:20

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
296
Chronic Kidney Disease I: Introduction01:25

Chronic Kidney Disease I: Introduction

Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
110