Related Experiment Video

Updated: Jul 14, 2026

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae
08:55

Assessment of Submitochondrial Protein Localization in Budding Yeast Saccharomyces cerevisiae

Published on: July 19, 2021

Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity, osmotic swelling and mitophagy

K Nowikovsky1, S Reipert, R J Devenish

  • 1Department of Genetics, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.

Cell Death and Differentiation
|June 2, 2007
PubMed

Insights

Loss of the MDM38 gene in yeast mitochondria causes osmotic swelling, triggering mitophagy. This process involves mitochondrial fragmentation and vacuole engulfment, which can be prevented by K(+)/H(+) ionophores.

Area of Science:

  • Mitochondrial biology
  • Cell biology
  • Molecular genetics

Background:

  • Mitochondria are vital organelles with complex functions, including energy production and cellular homeostasis.
  • The MDM38 gene product plays a crucial role in maintaining mitochondrial integrity and function.
  • Dysfunction in mitochondrial K(+)/H(+) exchange can lead to osmotic swelling and cellular damage.

Purpose of the Study:

  • To investigate the early events following the loss of MDM38 gene product in yeast mitochondria.
  • To elucidate the relationship between mitochondrial swelling, membrane potential, and mitophagy.
  • To determine the role of K(+)/H(+) exchange activity in mitochondrial morphology and autophagy.

Main Methods:

  • Utilized doxycycline-regulated gene expression to control MDM38 gene shut-off in yeast.
  • Employed a novel fluorescent biosensor to monitor mitochondrial matrix changes in real-time.
  • Assessed mitochondrial morphology, membrane potential, and protein content.
  • Investigated the effects of nigericin, a K(+)/H(+) ionophore, on mitochondrial function.

Main Results:

  • Loss of MDM38 gene product rapidly induced mitochondrial swelling, decreased membrane potential, and fragmentation of the mitochondrial reticulum.
  • Mitochondrial swelling was immediately followed by morphological changes in mitochondria and vacuoles, including their close association.
  • Uptake of mitochondrial material by vacuoles (mitophagy) was observed following MDM38 depletion.
  • Nigericin treatment fully prevented the observed swelling and subsequent mitophagy, indicating the critical role of K(+)/H(+) exchange.

Conclusions:

  • Osmotic swelling of mitochondria, triggered by the loss of MDM38 function, is an early event that initiates selective mitochondrial autophagy (mitophagy).
  • The K(+)/H(+) exchange activity is essential for maintaining mitochondrial osmotic balance and preventing mitophagy.
  • These findings provide insights into the mechanisms regulating mitochondrial quality control and cellular homeostasis.

More Related Videos

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue09:27

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

Related Concept Videos

Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...
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,...
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,...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
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...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...