Mitochondria, ancient endomembrane systems in eukaryotic cells, play a crucial role in ATP production through respiration. The evolution of mitochondria involved a significant reduction in their chromosome size and a shift in their behavior within cells. Recent studies have revealed how mitochondria have evolved to ensure accurate genome transmission and to respond to cellular needs and dysfunction. Mitochondria, arising from the engulfment of an α-proteobacterium by a precursor eukaryotic cell, have maintained their double membrane structure and ATP production capabilities while acquiring numerous additional functions. The human mitochondrial genome, a small circular molecule, encodes 13 proteins essential for respiratory complexes, which, along with the Krebs cycle, generate an electrochemical gradient that powers ATP synthesis via ATP synthase. This gradient also supports other mitochondrial functions, such as Ca2+ buffering. Modern mitochondria contain over 1,000 proteins, a mix of 'old' bacterial and 'new' eukaryotic-derived proteins. The mitochondrial proteome is regulated through transcriptional, posttranscriptional, and post translational mechanisms, with nuclear-encoded proteins translated on cytosolic ribosomes and imported into mitochondria via translocase machines. Mutations in mtDNA or nuclear genes encoding mitochondrial proteins can lead to a wide range of human diseases, including neurodegenerative disorders. The organization and transmission of the mitochondrial chromosome are complex, with mtDNA condensation facilitated by TFAM and replication and repair machinery. Mitochondrial division and fusion are critical for maintaining mtDNA copy number and distribution, and these processes are regulated by dynamin-related proteins (DRPs). The ER-associated mitochondrial division (ERMD) mechanism, involving the ER and mitochondria, is essential for mtDNA segregation and mitochondrial distribution. Mitochondrial dynamics are coordinated with other cellular processes, such as axonal transport in neurons, and are integrated with stress response pathways like UPRmt and mitophagy to maintain cellular homeostasis. Understanding the molecular basis of mitochondrial structure and behavior will provide insights into the fundamental processes of cellular organization and dysfunction.Mitochondria, ancient endomembrane systems in eukaryotic cells, play a crucial role in ATP production through respiration. The evolution of mitochondria involved a significant reduction in their chromosome size and a shift in their behavior within cells. Recent studies have revealed how mitochondria have evolved to ensure accurate genome transmission and to respond to cellular needs and dysfunction. Mitochondria, arising from the engulfment of an α-proteobacterium by a precursor eukaryotic cell, have maintained their double membrane structure and ATP production capabilities while acquiring numerous additional functions. The human mitochondrial genome, a small circular molecule, encodes 13 proteins essential for respiratory complexes, which, along with the Krebs cycle, generate an electrochemical gradient that powers ATP synthesis via ATP synthase. This gradient also supports other mitochondrial functions, such as Ca2+ buffering. Modern mitochondria contain over 1,000 proteins, a mix of 'old' bacterial and 'new' eukaryotic-derived proteins. The mitochondrial proteome is regulated through transcriptional, posttranscriptional, and post translational mechanisms, with nuclear-encoded proteins translated on cytosolic ribosomes and imported into mitochondria via translocase machines. Mutations in mtDNA or nuclear genes encoding mitochondrial proteins can lead to a wide range of human diseases, including neurodegenerative disorders. The organization and transmission of the mitochondrial chromosome are complex, with mtDNA condensation facilitated by TFAM and replication and repair machinery. Mitochondrial division and fusion are critical for maintaining mtDNA copy number and distribution, and these processes are regulated by dynamin-related proteins (DRPs). The ER-associated mitochondrial division (ERMD) mechanism, involving the ER and mitochondria, is essential for mtDNA segregation and mitochondrial distribution. Mitochondrial dynamics are coordinated with other cellular processes, such as axonal transport in neurons, and are integrated with stress response pathways like UPRmt and mitophagy to maintain cellular homeostasis. Understanding the molecular basis of mitochondrial structure and behavior will provide insights into the fundamental processes of cellular organization and dysfunction.