Related Experiment Video

Updated: Jan 21, 2026

Activating Autophagy by Aerobic Exercise in Mice
08:44

Activating Autophagy by Aerobic Exercise in Mice

Published on: February 3, 2017

12.7K

mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and

Matteo Bordi1,2,3, Sandipkumar Darji4, Yutaka Sato4

  • 1Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA. matteobordi@gmail.com.

Cell Death & Disease
|July 24, 2019
PubMed

Insights

Down syndrome (DS) involves mitochondrial damage due to deficient mitophagy. Inhibiting mTORC1/mTORC2 restores mitophagy, clearing damaged mitochondria and reducing oxidative stress, offering a potential therapy for DS.

Area of Science:

  • Cell Biology
  • Genetics
  • Biochemistry

Background:

  • Down syndrome (DS) is linked to mitochondrial dysfunction and damaged mitochondria accumulation.
  • Mitophagy, crucial for clearing damaged mitochondria, is impaired in DS.

Purpose of the Study:

  • To investigate the molecular mechanisms behind mitophagy deficiency in Down syndrome.
  • To explore potential therapeutic strategies targeting mitophagy in DS.

Main Methods:

  • Primary human fibroblasts from individuals with DS were analyzed.
  • Investigated PINK1/PARKIN pathway and macroautophagy regulation by mTOR.
  • Utilized AZD8055 to inhibit mTORC1/mTORC2.

Main Results:

  • DS fibroblasts exhibit impaired mitophagy and increased oxidative stress.
  • Downregulated PARKIN and p62, and hyperactivated mTOR were identified as key factors.
  • mTORC1/mTORC2 inhibition by AZD8055 restored mitophagy and cleared damaged mitochondria.

Conclusions:

  • Mitophagy deficiency in DS stems from PINK1/PARKIN impairment and mTOR-driven macroautophagy suppression.
  • Targeting mTORC1/mTORC2 with inhibitors like AZD8055 shows therapeutic promise for Down syndrome by restoring mitochondrial quality control.

More Related Videos

Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond09:00

Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond

Published on: July 27, 2013

19.2K
A Fluorescence Microscopy Assay for Monitoring Mitophagy in the Yeast Saccharomyces cerevisiae10:27

A Fluorescence Microscopy Assay for Monitoring Mitophagy in the Yeast Saccharomyces cerevisiae

Published on: July 18, 2011

26.1K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.4K
Attention-Deficit/Hyperactivity Disorder01:30

Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity. It affects approximately 5-8% of children globally, with around 60-70% of cases persisting into adulthood. ADHD has significant implications for educational attainment, social interactions, and occupational success.
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
810
Induction01:16

Induction

An emf is induced when the magnetic field in a coil is changed by pushing a bar magnet into or out of the coil. emfs of opposite signs are produced by motion in opposite directions, and the directions of emfs are also reversed by reversing poles. The same results are produced if the coil is moved rather than the magnet—it is the relative motion that is important. The faster the motion, the greater the emf. Additionally, there is no emf when the magnet is stationary relative to the coil.
A...
5.6K
Formation of Species01:31

Formation of Species

Speciation describes the formation of one or more new species from one or sometimes multiple original species. The resulting species are discrete from the parent species, and barriers to reproduction will typically exist. There are two primary mechanisms, speciation with and without geographic isolation—allopatric and sympatric speciation, respectively.
44.7K