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Updated: Apr 27, 2026

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General lysosomal hydrolysis can process prorenin accurately.

Lucie K Xa1, Marie-Josée Lacombe2, Chantal Mercure2

  • 1Laboratories of Molecular Biochemistry of Hypertension and Division of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada; and.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|June 27, 2014
PubMed
Summary

Active renin production is not unique to kidney cells. Prorenin processing occurs in lysosomes of various cells, suggesting general hydrolysis, not a specific enzyme, activates renin.

Keywords:
endocrinologyhypertensionlysosomesproteolysisreninrenin-angiotensin system

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • Renin, an aspartyl protease, initiates the renin-angiotensin system and is synthesized as inactive prorenin.
  • Prorenin activation involves removing a prosegment, a process attributed to a specific prorenin-processing enzyme (PPE) in kidney juxtaglomerular (JG) cells.
  • Extrarenal tissues secrete only prorenin, raising questions about the specialized activation mechanism in JG cells.

Purpose of the Study:

  • To test the hypothesis that a JG cell-specific PPE is responsible for active renin production.
  • To investigate whether prorenin processing can occur in non-JG cells.

Main Methods:

  • Investigated candidate PPE expression levels in mouse kidneys during induced renin production.
  • Engineered mouse Ren1 prorenin for targeting to lysosomes in cultured HEK-293 cells.
  • Assessed prorenin processing and active renin stability in HEK cell lysosomes.

Main Results:

  • Induced renin production in mouse kidneys did not correlate with increased expression of candidate PPEs.
  • Engineered prorenin was accurately processed and stored in HEK cell lysosomes.
  • Active renin demonstrated high resistance to proteolytic degradation, and HEK cell lysosomes degraded artificial protein extensions.

Conclusions:

  • Prorenin processing is not exclusive to JG cells and can occur in classical vesicular lysosomes of heterologous cells.
  • Active renin production likely relies on general lysosomal hydrolysis rather than a specific PPE.
  • The lysosome-like granules within JG cells may facilitate renin activation through non-specific proteolytic activity.