Related Experiment Video
Updated: May 31, 2026
10:25
Dual-color Correlative Light and Electron Microscopy for the Visualization of Interactions between Mitochondria and Lysosomes
Published on: September 27, 2024
Mitochondria-lysosome coupling contributes to lysosome acidification and aging
Qingqing Liu1, Seungmin Yoo1, Zhixin A Zhang1
1Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA.
Molecular Cell
|May 29, 2026
Summary
Mitochondria and lysosomes/vacuoles use membrane contacts to acidify cellular compartments. Disrupting these contacts causes de-acidification during aging, but restoring them reverses this effect, impacting senescence.
Area of Science:
- Cell Biology
- Biochemistry
- Aging Research
Background:
- Lysosomal (vacuolar in yeast) acidity is crucial for cellular functions like degradation and autophagy.
- Lysosome/vacuole acidification defects are linked to aging and age-related diseases.
- The conventional model posits proton (H⁺) import from the cytosol.
Purpose of the Study:
- To investigate a novel mechanism of lysosome/vacuole acidification.
- To explore the role of mitochondria-lysosome/vacuole contacts in maintaining pH homeostasis.
- To understand how aging affects lysosomal/vacuolar acidification and its potential reversal.
Main Methods:
- Utilized yeast and human cell models.
- Investigated mitochondria-lysosome/vacuole membrane contacts.
- Employed genetic engineering (engineered linker) and cell rejuvenation techniques.
Main Results:
- Discovered a conserved mechanism where mitochondria-lysosome/vacuole contacts facilitate proton (H⁺) uptake for acidification.
- Showed that aging disrupts these contacts, leading to lysosomal/vacuolar de-acidification.
- Demonstrated that restoring contacts or using specific rejuvenation processes reverses de-acidification.
- Preserving lysosomal acidity in senescent cells reduced senescence-associated secretory phenotype and restored autophagic flux.
Conclusions:
- Mitochondrial proton pumping via membrane contacts is a key mechanism for lysosome/vacuole acidification.
- Disruption of these contacts during aging impairs lysosomal function.
- Targeting mitochondria-lysosome/vacuole contacts offers a potential therapeutic strategy for aging and related diseases.
Related Concept Videos
01:37Mitochondria
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,...
01:37Mitochondria
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,...
01:19Translocation 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,...
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,...
01:36Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
01:31Lysosomes
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
01:31Lysosomes
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...