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II - Insulin processing in mitochondria.

María Del Carmen Camberos1, Adriana A Pérez2, Gisel A Passicot3

  • 1Endocrinology Research Center "Dr. Cesar Bergada" (CEDIE-CONICET), Endocrinology Division, Children Hospital. R. Gutierrez, Gallo 1330 (C1425), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. mccamberos@cedie.org.ar.

Journal of Bioenergetics and Biomembranes
|November 1, 2016
PubMed
Summary
This summary is machine-generated.

Mitochondria process insulin, with diet enhancing this degradation. High insulin levels do not cause accumulation in mitoplasts but suggest a transport system. ATP regulates mitochondrial insulin degradation.

Keywords:
ATP-dependent proteaseChromatography studiesIDE Insulin degradationMitochondrial fractionsSupplementary diet

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Area of Science:

  • Mitochondrial biology
  • Biochemistry
  • Endocrinology

Background:

  • Mitochondria play a role in cellular metabolism and signaling.
  • Insulin processing and degradation are critical for glucose homeostasis.
  • The precise mechanisms of insulin degradation within mitochondria remain incompletely understood.

Purpose of the Study:

  • To investigate insulin processing and degradation within mitochondria.
  • To determine if insulin-degrading enzyme (IDE) is the sole participant in mitochondrial insulin degradation.
  • To elucidate the role of insulin degradation in IDE accumulation within mitoplasts.

Main Methods:

  • Mitochondria and their fractions were isolated using Greenwalt's method.
  • Insulin-degrading enzyme (IDE) was purified and detected via immunoblot.
  • Insulin degradation was quantified using techniques including 5% TCA, insulin antibody, and Sephadex G50 chromatography.
  • Degradation assays were performed on mitochondrial fractions (IMS and Mx) with and without dietary modifications or IDE, and in fractions precipitated with ammonium sulfate.
  • The effect of ATP on degradation was assessed.

Main Results:

  • A supplementary diet significantly increased mitochondrial insulin degradation.
  • High insulin levels did not increase mitoplast accumulation or decrease mitochondrial degradation.
  • Evidence suggests insulin competes for a putative transport system into mitochondria.
  • Mitochondrial incubation with insulin led to increased IDE in the mitochondrial matrix.
  • ATP modulated insulin degradation, decreasing it in the matrix (Mx) and increasing it in the intermembrane space (IMS).
  • An ATP-dependent protease in the IMS was identified, capable of degrading insulin.

Conclusions:

  • Mitochondria actively participate in insulin degradation, a process enhanced by dietary changes.
  • Elevated insulin levels do not lead to mitochondrial degradation reduction or mitoplast accumulation.
  • Mitochondrial insulin degradation is regulated by ATP, with specific proteases involved.
  • Insulin transport into mitochondria may involve a competitive system.