[Changes in the outer mitochondrial membranes during apoptosis]

Safa Lucken-Ardjomande1, Sylvie Montessuit, Jean-Claude Martinou

  • 1Département de biologie cellulaire, Université de Genève, 30, quai Ernest-Ansermet, 1211 Genève 4, Suisse.

Insights

Mitochondria play a key role in apoptosis by releasing proteins that activate caspases. This review explores the proposed mechanisms behind mitochondrial outer membrane permeabilization during programmed cell death.

Area of Science:

  • Cell Biology
  • Biochemistry

Context:

  • Mitochondria are central regulators of apoptosis, a crucial process for cellular homeostasis and development.
  • The release of apoptogenic factors from mitochondria triggers downstream caspase cascades, leading to cell death.

Purpose:

  • To review and summarize proposed mechanisms of mitochondrial outer membrane permeabilization (MOMP).
  • To elucidate the molecular events leading to the release of cytochrome c and other pro-apoptotic factors.

Summary:

  • Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis, involving the formation of pores or rupture of the mitochondrial outer membrane.
  • This process allows the release of intermembrane space proteins, such as cytochrome c, into the cytosol.
  • Cytochrome c release initiates the formation of the apoptosome, activating caspase-9 and downstream executioner caspases.

Impact:

  • Understanding MOMP mechanisms is vital for developing targeted therapies for diseases involving dysregulated apoptosis, such as cancer and neurodegenerative disorders.
  • This review provides a consolidated overview of current knowledge, highlighting areas requiring further investigation in apoptotic signaling pathways.

Related Concept Videos

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,...
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,...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...