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Rab Cascades01:25

Rab Cascades

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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Rab Proteins01:14

Rab Proteins

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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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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...
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
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Rab14 promotes Parkin-mediated mitophagy.

Samina Momtaz1, Marco Padilla-Rodriguez2, Paola Cruz Flores3

  • 1Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724.

Molecular Biology of the Cell
|July 30, 2025
PubMed
Summary

Rab14 protein promotes mitophagy, a process essential for maintaining cell metabolism. This discovery reveals a new role for Rab14 in regulating mitochondrial quality control and cellular health.

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Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Autophagy

Background:

  • Mitophagy is crucial for cellular metabolism by removing damaged mitochondria.
  • Rab-GTPases are involved in vesicular trafficking and mitochondrial integrity.
  • The role of Rab14 in mitophagy was previously undescribed.

Purpose of the Study:

  • To investigate the role of Rab14, a trans-Golgi network (TGN)-endosomal Rab-GTPase, in mitophagy.
  • To elucidate the mechanism by which Rab14 influences mitochondrial quality control.

Main Methods:

  • Rab14 knockdown and overexpression studies.
  • Mito-Keima assays to measure mitophagy.
  • Analysis of mitophagy pathway components (Parkin, TBK1, PI3K).
  • 3D-reconstruction and TGN kinase inhibition.

Main Results:

  • Rab14 knockdown led to elongated mitochondria and increased mitochondrial proteins.
  • Rab14 overexpression enhanced mitophagy in a Parkin-dependent manner.
  • Rab14-mitochondria contact sites were observed, dependent on PI(4)KIIIβ activity.
  • TGN-derived Rab14 vesicles appear to mediate mitophagy.

Conclusions:

  • Rab14 plays a significant role in promoting mitophagy.
  • Rab14 is a key regulator of mitochondrial quality control and cellular metabolism.
  • TGN-derived vesicles are involved in Rab14-mediated mitophagy.