Mitochondrial cristae are the principal sites of oxidative phosphorylation and are central to mitochondria-dependent energy metabolism. Rather than static folds, cristae are dynamic bioenergetic compartments that remodel in response to physiological and stress cues. During remodeling, their number, length, width, lateral alignment, curvature/stiffness, and the geometry of crista junctions (CJs) can change. Depending on cellular context, cristae may increase in abundance, tighten or widen, and exhibit opening or closure of CJs, with corresponding effects on respiratory-chain organization and supercomplex assembly. Key regulators include OPA1 (and its proteolytic processing), the MICOS complex that scaffolds CJs, F₁Fo-ATP synthase dimerization/oligomerization that shapes high-curvature ridges, and cardiolipin, which stabilizes inner-membrane architecture. Abnormal cristae compromise electron transport, ATP production, and mitochondrial metabolism, contributing to neurodegeneration and metabolic disease etc. In this review, we synthesize current insights into the molecular control of cristae ultrastructure and its impact on mitochondrial metabolism, delineate structural features and quantitative readouts, and highlight mechanisms that govern cristae remodeling under physiological and stress conditions, with an emphasis on diseases arising from aberrant crista architecture.

Mitochondria are crucial for a wide range of cellular processes. One of the most important is innate immunity regulation. Apart from functioning as a signaling hub in immune reactions, mitochondrial nucleic acids can themselves act as damage-associated molecular patterns (DAMPs) to participate in immune processes directly. This review synthesizes the current understanding of mitochondrial RNA (mtRNA) biology and its link to immune activation through aberrant accumulation. We focus on its origin through bidirectional mitochondrial transcription and metabolism, encompassing maturation (cleavage, polyadenylation, modification) and degradation. Dysregulation of mtRNA metabolism leads to mt-dsRNA (mitochondrial double-stranded RNA) accumulation, which escapes mitochondria via specific channels into the cytosol and serves as DAMPs to trigger an immune response. We discuss the critical roles of key regulatory factors, including PNPT1 (PNPase, Polyribonucleotide Nucleotidyltrans ferase 1), in controlling mt-dsRNA levels and preventing inappropriate immune activation. Finally, we review the implications of mt-dsRNA-driven inflammation in human diseases, including autoimmune disorders, cellular senescence, and viral infection pathologies, highlighting unresolved questions regarding mt-dsRNA release mechanisms.