[Pathophysiology of human mitochondrial diseases]

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Context:

• Mitochondrial diseases are the most common inborn errors of metabolism.
• These diseases stem from defects in oxidative phosphorylation.
• Clinical presentations are highly diverse, making diagnosis difficult.

Purpose:

• To discuss the genetic origins of mitochondrial diseases.
• To explore the debated pathophysiological mechanisms.
• To explain the tissue-specificity of these disorders.

Summary:

• Diagnosis relies on inconstant and unspecific metabolic, histological, and enzymatic findings.
• Most mitochondrial diseases have genetic origins, involving numerous candidate genes in mitochondrial or nuclear DNA.
• Pathophysiological mechanisms, including gene expression, bioenergetic function, and heteroplasmic mitochondrial DNA distribution, are debated.

Impact:

• Improved understanding of mitochondrial disease mechanisms.
• Potential for more targeted diagnostic approaches.
• Foundation for future therapeutic strategies.