The elusive importance of being a mitochondrial Ca(2+) uniporter

Diana Pendin1, Elisa Greotti1, Tullio Pozzan2

  • 1Neuroscience Institute, National Research Council, Padova, Italy; Department of Biomedical Sciences, University of Padova, Italy.

Cell Calcium
|March 18, 2014
PubMed

Insights

Recent research has identified key molecular components of mitochondrial calcium (Ca2+) uptake, including the mitochondrial calcium uniporter (MCU) and MICU1. Studies reveal new subunits, a MCU knockout mouse model, and a human disease linked to MICU1 mutations.

Area of Science:

  • Cellular Biology
  • Mitochondrial Physiology
  • Molecular Medicine

Background:

  • The mitochondrial calcium (Ca2+) uptake machinery is crucial for cellular homeostasis.
  • Its molecular components have only recently been elucidated.
  • Understanding this complex is vital for addressing related diseases.

Purpose of the Study:

  • To summarize recent findings on the mitochondrial Ca2+ uptake complex.
  • To discuss the roles of newly identified subunits.
  • To explore contradictions and implications of recent discoveries.

Main Methods:

  • Literature review of recent findings on mitochondrial Ca2+ uptake.
  • Analysis of data from MCU knockout mouse models.
  • Examination of genetic human diseases linked to MICU1 mutations.

Main Results:

  • Identification of the pore-forming MCU and regulatory MICU1 subunits.
  • Description of four additional components of the mitochondrial Ca2+ uptake complex.
  • Generation of a MCU knockout mouse model and discovery of a human MICU1-related disease.

Conclusions:

  • The mitochondrial Ca2+ uptake complex is more intricate than previously thought.
  • Recent discoveries present both opportunities for understanding and areas of contradiction.
  • Further research is needed to reconcile findings and explore the unexpected results in MCU-KO mice.

Related Concept Videos

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...
2.0K
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...
3.5K
The ADP/ATP Carrier Protein01:42

The ADP/ATP Carrier Protein

ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
3.6K
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,...
8.8K
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...
4.4K
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
24.3K