Physical Contacts Between Mitochondria and WPBs Participate in WPB Maturation

Jing Ma1,2,3, Zhenhua Hao2,3, Yudong Zhang4,5

  • 1Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, China (J.M., Z.H., W.L.).

Abstract

Insights

Mitochondria physically contact Weibel-Palade bodies (WPBs) in endothelial cells. Rab3b mediates these contacts, which are essential for WPB maturation and von Willebrand factor secretion.

Area of Science:

  • Cell Biology
  • Organelle Biology
  • Endothelial Cell Function

Background:

  • Weibel-Palade bodies (WPBs) are specialized endothelial organelles vital for hemostasis, thrombosis, and inflammation.
  • WPBs store and release biologically active molecules, primarily von Willebrand factor (vWF).
  • Interactions between mitochondria and other organelles are known, but the mitochondrion-WPB relationship is unexplored.

Purpose of the Study:

  • To investigate the existence and nature of physical contacts between mitochondria and WPBs.
  • To determine the role of these interorganellar contacts in WPB function and biogenesis.

Main Methods:

  • Utilized electron microscopy and live-cell confocal microscopy to visualize mitochondrion-WPB interactions.
  • Developed an AI-assisted method for quantifying the duration and extent of organelle contact sites.
  • Investigated the role of Rab3b, a GTPase associated with WPBs, in mediating these contacts.

Main Results:

  • Confirmed direct physical contacts between mitochondria and WPBs in endothelial cells.
  • Observed that impaired mitochondrial function alters WPB morphology.
  • Identified Rab3b enrichment at mitochondrion-WPB contact sites, with Rab3b deficiency impairing WPB maturation and vWF secretion.

Conclusions:

  • Established that mitochondria and WPBs form physical contacts in endothelial cells.
  • Demonstrated that Rab3b is a key mediator of mitochondrion-WPB interactions.
  • Concluded that mitochondrion-WPB coupling is critical for proper WPB maturation and function.

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,...
3.1K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.0K
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K
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,...
11.2K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.4K
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.5K