Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

Angelika B Harbauer1, J Tabitha Hees2, Simone Wanderoy2

  • 1F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany; Institute of Neuronal Cell Biology, Technical University of Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster of Systems Neurology, Feodor-Lynen-Straße 17, 81377 Munich, Germany.

Neuron
|February 26, 2022
PubMed

Insights

Local translation of PTEN-induced kinase 1 (PINK1) mRNA near mitochondria enables mitophagy in neurons. This process ensures damaged mitochondria removal in distal neurites, crucial for neuronal health.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Mitochondrial Dynamics

Background:

  • PTEN-induced kinase 1 (PINK1) is vital for mitophagy, the process of removing damaged mitochondria.
  • PINK1's short half-life hinders its transport to neuronal processes, limiting mitophagy far from the cell body.

Purpose of the Study:

  • To investigate the mechanism enabling active mitophagy in distal neuronal compartments.
  • To understand how PINK1 is supplied to distant mitochondria for efficient damage removal.

Main Methods:

  • Analysis of Pink1 transcript localization and cotransport with neuronal mitochondria.
  • Investigation of the role of synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) in mRNA tethering.
  • Study of local translation of PINK1 in neurons.

Main Results:

  • The Pink1 transcript is cotransported with neuronal mitochondria.
  • SYNJ2BP and SYNJ2 tether Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2.
  • Local translation of PINK1 occurs on mitochondria in neurons.

Conclusions:

  • Neurons utilize a specialized mechanism for local PINK1 translation on mitochondria.
  • This adaptation ensures a continuous supply of PINK1 to distal mitochondria, supporting mitophagy.
  • This process is essential for maintaining neuronal health by clearing damaged mitochondria in neurites.

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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,...
6.3K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.6K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.1K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
2.7K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.2K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.6K