Changes of mitochondria and relocation of the apoptosis-inducing factor during apoptosis

A Ivana Scovassi1, Cristiana Soldani, Paola Veneroni

  • 1Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy. scovassi@igm.cnr.it

Insights

Apoptosis-inducing factor (AIF) translocates to the nucleus during early apoptosis. In late apoptosis, AIF remains primarily in mitochondria, separate from fragmented chromatin.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis-inducing factor (AIF) is a key protein involved in programmed cell death.
  • AIF is known to translocate from mitochondria to the nucleus during apoptosis.

Purpose of the Study:

  • To investigate the spatiotemporal dynamics of AIF during apoptosis in HeLa cells.
  • To analyze the relationship between AIF localization and chromatin changes in different stages of apoptosis.

Main Methods:

  • HeLa cells were induced into apoptosis using etoposide or actinomycin D.
  • Immunolabeling techniques were used to track the localization of AIF and cytochrome c.
  • Mitochondrial structure and function were assessed.

Main Results:

  • Mitochondrial alterations and translocation of cytochrome c and AIF to the nucleus were observed in early apoptosis.
  • In late apoptosis, with fragmented chromatin, AIF immunolabeling was distinct from chromatin and localized mainly to mitochondria.

Conclusions:

  • AIF exhibits dynamic localization changes during apoptosis, moving to the nucleus in early stages.
  • AIF's localization shifts back to mitochondria in late apoptosis, independent of chromatin fragmentation.

Related Concept Videos

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.
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,...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...