General pathology · Cell injury, adaptation and death
Mechanisms of cell injury: ATP, mitochondria, calcium, membranes and DNA !
- Mechanism
Most injuries act through a few shared paths: energy loss, broken mitochondria, excess calcium, free radicals, leaky membranes and DNA damage.
Updated 2026-11-01
What it is
Different injuries meet in a small set of biochemical routes. Loss of ATP stops pumps and synthesis; damaged mitochondria release death signals; excess cytosolic calcium switches on destructive enzymes; free radicals oxidize lipids, proteins and DNA; and damaged membranes let the cell leak. When DNA or proteins are damaged beyond repair, the cell usually chooses apoptosis.
Function
- ATP depletion: the Na⁺/K⁺ and Ca²⁺ pumps fail, the cell swells and calcium rises inside it.
- Mitochondrial injury: less ATP, more free radicals, and leak of pro-apoptotic proteins.
- Calcium overload: enzymes digest membranes, proteins and chromatin; more mitochondrial pores open.
- Oxidative stress: free radicals peroxidize membrane lipids and break DNA.
- Membrane damage: loss of the ion barrier, release of lysosomal enzymes and leak of cell contents.
- DNA and protein damage: p53 or the unfolded protein response push the cell toward apoptosis.
Step by step
- An insult (hypoxia, toxin, radiation, infection) hits one or more cell targets.
- ATP falls as oxidative phosphorylation fails; pumps stop and the cell swells.
- Calcium floods the cytosol from outside and from the ER and mitochondria.
- Calcium-activated enzymes and free radicals damage membranes, proteins and DNA.
- Mitochondria lose their membrane potential and release cytochrome c.
- Mild damage leads to apoptosis; massive damage with membrane rupture leads to necrosis.
Clinical notes
- Cyanide blocks cytochrome c oxidase (complex IV): cells cannot use oxygen and the venous blood stays bright red.
- Inherited mitochondrial diseases (MELAS, Leigh syndrome) hurt organs with high energy needs: brain, muscle and heart.
Test yourself
Think of the answer, then tap the question to see it.
Which enzymes does an increase in cytosolic calcium activate?
Phospholipases, proteases, endonucleases and ATPases, which damage membranes, the cytoskeleton, chromatin and further deplete ATP.
Why does anaerobic glycolysis during ischemia lead to chromatin clumping?
It produces lactic acid and lowers the intracellular pH, which causes the nuclear chromatin to clump.
What does a cell usually do when its DNA damage cannot be repaired?
p53 accumulates, arrests the cell cycle and, if repair fails, triggers apoptosis by the intrinsic pathway.
Related
- Reversible vs irreversible cell injury: the point of no return
- Oxidative stress and free-radical injury
- Hypoxia, ischemia and reperfusion injury
- Apoptosis: the intrinsic and extrinsic pathways
- Endoplasmic reticulum stress and the unfolded protein response
Related conditions
- Myocardial Infarction (Heart Attack)
- Ischaemic stroke
- Cyanide poisoning
- Carbon monoxide poisoning
- MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)
- Leigh syndrome
- Leber hereditary optic neuropathy (LHON)
- Acute kidney injury
- Malignant hyperthermia
Elsewhere in DurgiPedia
- Electron transport chain and oxidative phosphorylation
- IP₃, DAG and calcium pathway
- Na⁺/K⁺-ATPase (sodium pump)
- Cytochrome c
- ATP (adenosine triphosphate)
- Cell volume regulation
- Organelles: nucleus, ER, Golgi, mitochondria, lysosomes, peroxisomes
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: What is a cell?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2024); Mitochondrial Diseases: MedlinePlus (MedlinePlus, US National Library of Medicine, 2024); Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024).
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Representative model, for educational purposes only.