21: Elucidate three different pathways for targeting proteins to the mitochondrial inner membrane. NOTE: PLEASE CITE SOURCES Solution Answer: Protein translocation across mitochondrial membranes is mediated by multi-subunit protein complexes that function as protein translocators: 1. TOM complex: functions across the outer membrane 2. TIM23 and TIM22 complexes: function across the inner membrane 3. OXA complex TOM and TIM stand for translocase of the outer and inner mitochondrial membranes, respectively. These complexes contain some components that act as receptors for mitochondrial precursor proteins and other components that form the translocation channel. The TOM complex is required for the import of all nucleus-encoded mitochondrial proteins. It initially transports their signal sequences into the intermembrane space and helps to insert transmembrane proteins into the outer membrane. The TIM23 complex then transports some of these proteins into the matrix space, while helping to insert transmembrane proteins into the inner membrane. The TIM22 complex mediates the insertion of a subclass of inner membrane proteins, including the carrier protein that transports ADP, ATP, and phosphate. A third protein translocator in the inner mitochondrial membrane, the OXA complex, mediates the insertion of inner membrane proteins that are synthesized within the mitochondria. It also helps to insert some proteins that are initially transported into the matrix by the TOM and TIM complexes. Citations: 1. Stefan A. Paschen and Walter Neuper. Protein Import Into Mitochondria. IUBMB Life, 52: 101–11 (2001) 2. Dejana Mokranjac and Walter Neupert. The many faces of the mitochondrial TIM23 complex. Biochimica et Biophysica Acta. 1797, 1045–1054 (2010).

1. 21: Elucidate three different pathways for targeting proteins to the mitochondrial inner
membrane.
NOTE: PLEASE CITE SOURCES
Solution
Answer:
Protein translocation across mitochondrial membranes is mediated by multi-subunit protein
complexes that function as protein translocators:
1. TOM complex: functions across the outer membrane
2. TIM23 and TIM22 complexes: function across the inner membrane
3. OXA complex
TOM and TIM stand for translocase of the outer and inner mitochondrial membranes,
respectively. These complexes contain some components that act as receptors for mitochondrial
precursor proteins and other components that form the translocation channel.
The TOM complex is required for the import of all nucleus-encoded mitochondrial proteins. It
initially transports their signal sequences into the intermembrane space and helps to insert
transmembrane proteins into the outer membrane. The TIM23 complex then transports some of
these proteins into the matrix space, while helping to insert transmembrane proteins into the
inner membrane.
The TIM22 complex mediates the insertion of a subclass of inner membrane proteins, including
the carrier protein that transports ADP, ATP, and phosphate.
A third protein translocator in the inner mitochondrial membrane, the OXA complex, mediates
the insertion of inner membrane proteins that are synthesized within the mitochondria. It also
helps to insert some proteins that are initially transported into the matrix by the TOM and TIM
complexes.
Citations:
1. Stefan A. Paschen and Walter Neuper. Protein Import Into Mitochondria. IUBMB Life, 52:
101–11 (2001)
2. Dejana Mokranjac and Walter Neupert. The many faces of the mitochondrial TIM23 complex.
Biochimica et Biophysica Acta. 1797, 1045–1054 (2010)